, Volume 51, Issue 7, pp 1306-1316
Date: 24 Apr 2008

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

Abstract

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.

S. Franckhauser, I. Elias and V. Rotter Sopasakis contributed equally to this study.