Published in:
01-11-2010 | Article
Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance
Authors:
V. B. Matthews, T. L. Allen, S. Risis, M. H. S. Chan, D. C. Henstridge, N. Watson, L. A. Zaffino, J. R. Babb, J. Boon, P. J. Meikle, J. B. Jowett, M. J. Watt, J.-O. Jansson, C. R. Bruce, M. A. Febbraio
Published in:
Diabetologia
|
Issue 11/2010
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Abstract
Aims/hypothesis
The role of IL-6 in the development of obesity and hepatic insulin resistance is unclear and still the subject of controversy. We aimed to determine whether global deletion of Il6 in mice (Il6
−/−) results in standard chow-induced and high-fat diet (HFD)-induced obesity, hepatosteatosis, inflammation and insulin resistance.
Methods
Male, 8-week-old Il6
−/− and littermate control mice were fed a standard chow or HFD for 12 weeks and phenotyped accordingly.
Results
Il6
−/− mice displayed obesity, hepatosteatosis, liver inflammation and insulin resistance when compared with control mice on a standard chow diet. When fed a HFD, the Il6
−/− and control mice had marked, equivalent gains in body weight, fat mass and ectopic lipid deposition in the liver relative to chow-fed animals. Despite this normalisation, the greater liver inflammation, damage and insulin resistance observed in chow-fed Il6
−/− mice relative to control persisted when both were fed the HFD. Microarray analysis from livers of mice fed a HFD revealed that genes associated with oxidative phosphorylation, the electron transport chain and tricarboxylic acid cycle were uniformly decreased in Il6
−/− relative to control mice. This coincided with reduced maximal activity of the mitochondrial enzyme β-hydroxyacyl-CoA-dehydrogenase and decreased levels of mitochondrial respiratory chain proteins.
Conclusions/interpretation
Our data suggest that IL-6 deficiency exacerbates HFD-induced hepatic insulin resistance and inflammation, a process that appears to be related to defects in mitochondrial metabolism.