Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance

Diabetologia. 2010 Nov;53(11):2431-41. doi: 10.1007/s00125-010-1865-y. Epub 2010 Aug 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Adiposity / genetics
  • Animals
  • Body Composition / genetics
  • Calorimetry, Indirect
  • Cell Size
  • Diglycerides / metabolism
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Female
  • Inflammation / genetics*
  • Insulin Resistance / genetics*
  • Interleukin-6 / deficiency*
  • Interleukin-6 / genetics
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / genetics
  • Obesity / metabolism
  • Triglycerides / metabolism


  • Diglycerides
  • Interleukin-6
  • Triglycerides