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Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance
Citation
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 Statement
Copyright 2010 Springer-Verlag
DOI: doi:10.1007/s00125-010-1865-y
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.
Item Details
Item Type: | Refereed Article |
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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 Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Henstridge, DC (Dr Darren Henstridge) |
ID Code: | 133329 |
Year Published: | 2010 |
Web of Science® Times Cited: | 238 |
Deposited By: | Health Sciences |
Deposited On: | 2019-06-24 |
Last Modified: | 2019-07-23 |
Downloads: | 0 |
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