Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone
Abstract
IL-6 has emerged as an important cytokine upregulated in states of insulin resistance such as type 2 diabetes. We evaluated the chronic effect of IL-6 on insulin signaling in 3T3-F442A and 3T3-L1 adipocytes. First, cells responded to a chronic treatment with IL-6 by initiating an autoactivation process that increased IL-6 secretion. Second, IL-6-treated adipocytes showed a decreased protein expression of IR-beta subunit and IRS-1 but also an inhibition of the insulin-induced activation of IR-beta, Akt/PKB, and ERK1/2. Moreover, IL-6 suppressed the insulin-induced lipogenesis and glucose transport consistent with a diminished expression of GLUT4. IL-6-treated adipocytes failed to maintain their adipocyte phenotype as shown by the downregulation of the adipogenic markers FAS, GAPDH, aP2, PPAR-gamma, and C/EBP-alpha. IL-6 also induced the expression of SOCS-3, a potential inhibitor of insulin signaling. Finally, the effects of IL-6 could be prevented by rosiglitazone, an insulin-sensitizing agent. Thus, IL-6 may play an important role in the set-up of insulin resistance in adipose cell.
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Gene expression of MCP-1, colony-stimulating factor-3 and urokinase plasminogen activator CD87 increases significantly in adipose tissue of subjects with morbid obesity.
“Gene expression studies with human adipose tissue have demonstrated that the levels of expression of MCP-1, colony-stimulating factor-3 and the urokinase plasminogen activator CD87 increase significantly in the adipose tissue of subjects with morbid obesity (31) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [31]
In obese subjects, macrophages typically aggregate in crowns around apoptotic adipocytes.
“In obese subjects, these macrophages typically aggregate in crowns around apoptotic adipocytes (31) (Figs. 1 and 2).”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [31]
HIF-1a is overexpressed in subcutaneous adipose tissue of obese subjects and decreases during weight reduction.
“Hypoxia-inducible factor-1a, a transcription factor normally induced by hypoxia, is overexpressed in the subcutaneous adipose tissue of obese subjects and its expression is decreased during weight reduction (31) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [31]
Increased IL-10 protein expression after weight loss suggests a possible M1 to M2 macrophage phenotype switch.
“In this study, the protein expression of IL-10 increased, suggesting a possible M1 to M2 (pro-inflammatory to anti-inflammatory) switch of macrophage phenotypes (31) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [31]
Reduced secretion of pro-inflammatory mediators from adipocytes or adipose tissue macrophages likely contributes to the effect of weight loss.
“On the other hand, it seems likely that reduced secretion of pro-inflammatory mediators from adipocytes or activated macrophages of adipose tissue contributes to the effect of weight loss (31,36,65,67,142) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [31]
The parallelism between down-regulation of inflammation-related genes and reduction in adiposity and adipocyte diameter by n-3 PUFA treatment suggests a positive relationship between adipose cell size and adipose tissue inflammation.
“The parallelism between the down-regulation of these genes and the reduction in adiposity and adipocyte diameter by n-3 PUFA treatment suggests a positive relationship between adipose cell size and adipose tissue inflammation, agreeing with other observations (31,66) .”
From Dietary factors and low-grade inflammation in relation to overweight and obesity (2011) · cites this paper as [31]
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- Authors
- Lagathu, C., Bastard, J.-P., Auclair, M., Maachi, M., Capeau, J., & Caron, M.
- Affiliations
- Inserm (FR)
- Corresponding author
- Caron, Martine
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 311
- Issue
- 2
- Pages
- 372-379
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2061613314
- Cited by
- 385
- References
- 45
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 15 · 2023: 11 · 2022: 15 · 2021: 9 · 2020: 12 · 2019: 6 · 2018: 13 · 2017: 17 · 2016: 16 · 2015: 12 · 2014: 17 · 2013: 25 · 2012: 29
- FWCI
- 16.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- 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
- interleukin-6, insulin resistance, adipocytes, rosiglitazone, insulin signaling, insulin receptor beta, IRS-1, Akt, ERK1/2, GLUT4, lipogenesis, adipogenesis, SOCS3, type 2 diabetes, 3T3-L1 cells
- MeSH terms
- Suppressor of Cytokine Signaling 3 Protein, Rosiglitazone, Animals, Dose-Response Relationship, Drug, Glucose, Insulin Resistance, Proteins, Repressor Proteins, Transcription Factors, Signal Transduction, Interleukin-6, Up-Regulation, 3T3 Cells, Adipocytes, 3T3-L1 Cells, Thiazolidinediones, Suppressor of Cytokine Signaling Proteins, Mice
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