Cited by 385Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone

Lagathu, Claire, Bastard, Jean-Philippe, Auclair, Martine, Maachi, Mustapha, Capeau, Jacqueline, Caron, Martine·2003·Biochemical and Biophysical Research Communications

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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Crossref · 10.1016/j.bbrc.2003.10.013

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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) .”
  • 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).”
  • 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) .”
  • 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) .”
  • 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) .”

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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
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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