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

(2010) CELL METABOLISM. 12(3). p.237-249
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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.
Keywords
SKELETAL-MUSCLE, GLUCOSE-PRODUCTION, NECROSIS-FACTOR-ALPHA, ADIPOSE-TISSUE, RHEUMATOID-ARTHRITIS, EXPRESSING NEURONS, NITRIC-OXIDE, DOUBLE-BLIND, IKK-BETA, IN-VIVO

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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.
@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},
}

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