Overexpression of Il6 leads to hyperinsulinaemia, liver inflammation and reduced body weight in mice

Diabetologia. 2008 Jul;51(7):1306-16. doi: 10.1007/s00125-008-0998-8. Epub 2008 Apr 24.


Aims/hypothesis: IL-6 is released by the adipose tissue and increased circulating levels in obesity are associated with hyperinsulinaemia and insulin resistance. Short-term experiments suggest that increased IL-6 release by the skeletal muscle following exercise may improve insulin sensitivity.

Methods: In order to examine the effect of chronically elevated IL-6 levels, we overexpressed Il6 in skeletal muscle in mice using an electro-transfer procedure.

Results: Circulating IL-6 levels were increased and the animals rapidly lost both weight and body fat, but food intake was unchanged, which is consistent with the finding that IL-6 increased energy expenditure. Insulin levels were inappropriately elevated and combined with hypoglycaemia in spite of reduced 2-deoxy-D: -glucose uptake by skeletal muscle. Insulin-stimulated glucose uptake by skeletal muscles ex vivo was reduced, probably due to the decreased amounts of glucose transporter (GLUT)-4. Beta cell insulin content was increased, while apparent beta cell mass was unchanged. Circulating serum amyloid A cluster levels were increased tenfold due to a pronounced proinflammatory state in the liver with infiltration of inflammatory cells. However, no liver steatosis was found, which may be accounted for by concomitant AMP kinase activation.

Conclusions/interpretation: Chronically elevated IL-6 levels lead to inappropriate hyperinsulinaemia, reduced body weight, impaired insulin-stimulated glucose uptake by the skeletal muscles and marked inflammation in the liver. Thus, the pleiotrophic effects of chronically elevated IL-6 levels preclude any obvious usefulness in treating obesity or its associated metabolic complications in man, despite the fact that weight reduction may be expected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylate Kinase / metabolism
  • Adipose Tissue / physiology
  • Animals
  • Body Weight / genetics
  • Chimera
  • Cytomegalovirus / genetics
  • Deoxyglucose / pharmacokinetics
  • Gene Expression / immunology
  • Glucose / metabolism
  • Glucose Transporter Type 4 / metabolism
  • Hepatitis / genetics*
  • Hepatitis / immunology
  • Hepatitis / physiopathology*
  • Hyperinsulinism / genetics*
  • Hyperinsulinism / immunology
  • Hyperinsulinism / physiopathology*
  • Insulin Resistance / genetics
  • Insulin Resistance / immunology
  • Interleukin-6 / blood
  • Interleukin-6 / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Muscle, Skeletal / physiology
  • Phosphorylation


  • Glucose Transporter Type 4
  • Interleukin-6
  • Slc2a4 protein, mouse
  • Deoxyglucose
  • Adenylate Kinase
  • Glucose