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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 UGent, et al. (2010) CELL METABOLISM. 12(3). p.237-249
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) a deficiency (IL-6RaL-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-6Ra-disruption caused an exaggerated inflammatory response during euglycemic hyperinsulinemic clamp analysis, as revealed by increased expression of IL-6, TNF-a, and IL-10, as well as enhanced activation of inflammatory signaling such as phosphorylation of IkBa. Neutralization of TNF-a or ablation of Kupffer cells restored glucose tolerance in IL-6RaL-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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
SKELETAL-MUSCLE, GLUCOSE-PRODUCTION, NECROSIS-FACTOR-ALPHA, ADIPOSE-TISSUE, RHEUMATOID-ARTHRITIS, EXPRESSING NEURONS, NITRIC-OXIDE, DOUBLE-BLIND, IKK-BETA, IN-VIVO
journal title
CELL METABOLISM
Cell Metab.
volume
12
issue
3
pages
237 - 249
Web of Science type
Article
Web of Science id
000281703300008
JCR category
ENDOCRINOLOGY & METABOLISM
JCR impact factor
18.207 (2010)
JCR rank
2/115 (2010)
JCR quartile
1 (2010)
ISSN
1550-4131
DOI
10.1016/j.cmet.2010.06.011
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1045910
handle
http://hdl.handle.net/1854/LU-1045910
date created
2010-09-24 16:46:19
date last changed
2016-12-19 15:46:28
@article{1045910,
  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) a deficiency (IL-6RaL-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-6Ra-disruption caused an exaggerated inflammatory response during euglycemic hyperinsulinemic clamp analysis, as revealed by increased expression of IL-6, TNF-a, and IL-10, as well as enhanced activation of inflammatory signaling such as phosphorylation of IkBa. Neutralization of TNF-a or ablation of Kupffer cells restored glucose tolerance in IL-6RaL-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.},
  author       = {Wunderlich, F Thomas and Str{\"o}hle, Peter and K{\"o}nner, A Christine and Gruber, Sabine and Tovar, Sulay and Br{\"o}nneke, Hella S and Juntti-Berggren, Lisa and Li, Luo-Sheng and van Rooijen, Nico and Libert, Claude and Berggren, Per-Olof and Br{\"u}ning, Jens C},
  issn         = {1550-4131},
  journal      = {CELL METABOLISM},
  keyword      = {SKELETAL-MUSCLE,GLUCOSE-PRODUCTION,NECROSIS-FACTOR-ALPHA,ADIPOSE-TISSUE,RHEUMATOID-ARTHRITIS,EXPRESSING NEURONS,NITRIC-OXIDE,DOUBLE-BLIND,IKK-BETA,IN-VIVO},
  language     = {eng},
  number       = {3},
  pages        = {237--249},
  title        = {Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action},
  url          = {http://dx.doi.org/10.1016/j.cmet.2010.06.011},
  volume       = {12},
  year         = {2010},
}

Chicago
Wunderlich, F Thomas, Peter Ströhle, A Christine Könner, Sabine Gruber, Sulay Tovar, Hella S Brönneke, Lisa Juntti-Berggren, et al. 2010. “Interleukin-6 Signaling in Liver-parenchymal Cells Suppresses Hepatic Inflammation and Improves Systemic Insulin Action.” Cell Metabolism 12 (3): 237–249.
APA
Wunderlich, F. T., Ströhle, P., Könner, A. C., Gruber, S., Tovar, S., Brönneke, H. S., Juntti-Berggren, L., et al. (2010). Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action. CELL METABOLISM, 12(3), 237–249.
Vancouver
1.
Wunderlich FT, Ströhle P, Könner AC, Gruber S, Tovar S, Brönneke HS, et al. Interleukin-6 signaling in liver-parenchymal cells suppresses hepatic inflammation and improves systemic insulin action. CELL METABOLISM. 2010;12(3):237–49.
MLA
Wunderlich, F Thomas, Peter Ströhle, A Christine Könner, et al. “Interleukin-6 Signaling in Liver-parenchymal Cells Suppresses Hepatic Inflammation and Improves Systemic Insulin Action.” CELL METABOLISM 12.3 (2010): 237–249. Print.