Wunderlich, F. Thomas, Stroehle, Peter, Koenner, A. Christine, Gruber, Sabine, Tovar, Sulay ORCID: 0000-0001-7813-6520, Broenneke, Hella S., Juntti-Berggren, Lisa, Li, Luo-Sheng, van Rooijen, Nico, Libert, Claude, Berggren, Per-Olof ORCID: 0000-0001-8991-413X and Bruening, Jens C. (2010). Interleukin-6 Signaling in Liver-Parenchymal Cells Suppresses Hepatic Inflammation and Improves Systemic Insulin Action. Cell Metab., 12 (3). S. 237 - 250. CAMBRIDGE: CELL PRESS. ISSN 1932-7420

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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) alpha deficiency (IL-6R alpha(L-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-6R alpha-disruption caused an exaggerated inflammatory response during euglycemic hyperinsulinemic clamp analysis, as revealed by increased expression of IL-6, TNF-alpha, and IL-10, as well as enhanced activation of inflammatory signaling such as phosphorylation of I kappa B alpha. Neutralization of TNF-alpha or ablation of Kupffer cells restored glucose tolerance in IL-6R alpha(L-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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wunderlich, F. ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stroehle, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koenner, A. ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruber, SabineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tovar, SulayUNSPECIFIEDorcid.org/0000-0001-7813-6520UNSPECIFIED
Broenneke, Hella S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Juntti-Berggren, LisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, Luo-ShengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Rooijen, NicoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Libert, ClaudeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berggren, Per-OlofUNSPECIFIEDorcid.org/0000-0001-8991-413XUNSPECIFIED
Bruening, Jens C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-496650
DOI: 10.1016/j.cmet.2010.06.011
Journal or Publication Title: Cell Metab.
Volume: 12
Number: 3
Page Range: S. 237 - 250
Date: 2010
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1932-7420
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NECROSIS-FACTOR-ALPHA; SKELETAL-MUSCLE; GLUCOSE-PRODUCTION; ADIPOSE-TISSUE; RHEUMATOID-ARTHRITIS; EXPRESSING NEURONS; NITRIC-OXIDE; DOUBLE-BLIND; IKK-BETA; IN-VIVOMultiple languages
Cell Biology; Endocrinology & MetabolismMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/49665

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