Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action

F. Thomas Wunderlich, Peter Ströhle, A. Christine Könner, Sabine Gruber, Sulay Tovar, Hella S. Brönneke, Lisa Juntti-Berggren, Luo Sheng Li, Nico Van Rooijen, Claude Libert, Per Olof Berggren, Jens C. Brüning

Research output: Contribution to journalArticle

130 Citations (Scopus)

Abstract

The contribution of interleukin (IL)-6 signaling in obesity-induced inflammation remains controversial. To specifically define the role of hepatic IL-6 signaling in insulin action and resistance, we have generated mice with hepatocyte-specific IL-6 receptor (IL-6R) α deficiency (IL-6RαL-KO mice). These animals showed no alterations in body weight and fat content but exhibited a reduction in insulin sensitivity and glucose tolerance. Impaired glucose metabolism originated from attenuated insulin-stimulated glucose transport in skeletal muscle and fat. Surprisingly, hepatic IL-6Rα-disruption caused an exaggerated inflammatory response during euglycemic hyperinsulinemic clamp analysis, as revealed by increased expression of IL-6, TNF-α, and IL-10, as well as enhanced activation of inflammatory signaling such as phosphorylation of IκBα. Neutralization of TNF-α or ablation of Kupffer cells restored glucose tolerance in IL-6RαL-KO mice. Thus, our results reveal an unexpected role for hepatic IL-6 signaling to limit hepatic inflammation and to protect from local and systemic insulin resistance.

Original languageEnglish
Pages (from-to)237-249
Number of pages13
JournalCell Metabolism
Volume12
Issue number3
DOIs
StatePublished - Sep 8 2010
Externally publishedYes

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Hepatocytes
Interleukins
Interleukin-6
Insulin
Inflammation
Insulin Resistance
Glucose
Liver
Interleukin-6 Receptors
Glucose Clamp Technique
Kupffer Cells
Interleukin-10
Adipose Tissue
Skeletal Muscle
Obesity
Fats
Body Weight
Phosphorylation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Wunderlich, F. T., Ströhle, P., Könner, A. C., Gruber, S., Tovar, S., Brönneke, H. S., ... Brüning, J. C. (2010). Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action. Cell Metabolism, 12(3), 237-249. https://doi.org/10.1016/j.cmet.2010.06.011

Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action. / Wunderlich, F. Thomas; Ströhle, Peter; Könner, A. Christine; Gruber, Sabine; Tovar, Sulay; Brönneke, Hella S.; Juntti-Berggren, Lisa; Li, Luo Sheng; Van Rooijen, Nico; Libert, Claude; Berggren, Per Olof; Brüning, Jens C.

In: Cell Metabolism, Vol. 12, No. 3, 08.09.2010, p. 237-249.

Research output: Contribution to journalArticle

Wunderlich, FT, Ströhle, P, Könner, AC, Gruber, S, Tovar, S, Brönneke, HS, Juntti-Berggren, L, Li, LS, Van Rooijen, N, Libert, C, Berggren, PO & Brüning, JC 2010, 'Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action', Cell Metabolism, vol. 12, no. 3, pp. 237-249. https://doi.org/10.1016/j.cmet.2010.06.011
Wunderlich, F. Thomas ; Ströhle, Peter ; Könner, A. Christine ; Gruber, Sabine ; Tovar, Sulay ; Brönneke, Hella S. ; Juntti-Berggren, Lisa ; Li, Luo Sheng ; Van Rooijen, Nico ; Libert, Claude ; Berggren, Per Olof ; Brüning, Jens C. / Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action. In: Cell Metabolism. 2010 ; Vol. 12, No. 3. pp. 237-249.
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