Matthews, VB and Allen, TL and Risis, S and Chan, MHS and Henstridge, DC and Watson, N and Zaffino, LA and Babb, JR and Boon, J and Meikle, PJ and Jowett, JB and Watt, MJ and Jansson, J-O and Bruce, CR and Febbraio, MA, Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance, Diabetologia, 53, (11) pp. 2431-2441. ISSN 0012-186X (2010) [Refereed Article]
Copyright 2010 Springer-Verlag
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.
|Item Type:||Refereed Article|
|Keywords:||cytokines, fatty liver, obesity, signal transduction, type 2 diabetes, 3 hydroxyacyl coenzyme A dehydrogenase, interleukin 6, animal experiment, animal model, animal tissue, anthropometric parameters, article, citric acid cycle, controlled study|
|Research Division:||Biological Sciences|
|Research Group:||Biochemistry and cell biology|
|Research Field:||Cell metabolism|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Henstridge, DC (Mr Darren Henstridge)|
|Web of Science® Times Cited:||223|
|Deposited By:||Health Sciences|
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