Interleukin-6-deficient mice develop mature-onset obesity

Abstract

The immune-modulating cytokine interleukin-6 (IL-6) is expressed both in adipose tissue and centrally in hypothalamic nuclei that regulate body composition. We investigated the impact of loss of IL-6 on body composition in mice lacking the gene encoding IL-6 (Il6−/− mice) and found that they developed mature-onset obesity that was partly reversed by IL-6 replacement. The obese Il6−/− mice had disturbed carbohydrate and lipid metabolism, increased leptin levels and decreased responsiveness to leptin treatment. To investigate the possible mechanism and site of action of the anti-obesity effect of IL-6, we injected rats centrally and peripherally with IL-6 at low doses. Intracerebroventricular, but not intraperitoneal IL-6 treatment increased energy expenditure. In conclusion, centrally acting IL-6 exerts anti-obesity effects in rodents.

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Figure 1: Il6−/− mice develop mature-onset obesity and decreased glucose tolerance.
Figure 2: Increased leptin levels and leptin resistance in older Il6−/− mice.
Figure 3: IL-6 replacement therapy decreases obesity in obese Il6−/− mice.
Figure 4: Intracerebroventricular IL-6 treatment increases oxygen consumption and carbon dioxide production.

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Acknowledgements

We thank M. Kopf for the Il6−/− mice; J. Borén for the measurements of triglycerides; P. Lindström for mouse plasma samples; L. Lönn for valuable advice regarding adipose tissue measurements with CT; L. Kvist, M. Petterson, L. Bengtsson, L. Svensson and I. Berglund-Dahl for technical assistance; and our project student A. Leffler. This study was supported by grants from the European Comission (Framework 5, QLRT-1999-02038), Swedish Research Council (9894, 6834), the Swedish Foundation for International Cooperation in Research and Higher Education (STINT), Bergvall Foundation, Assar Gabrielsson Foundation, Grönberg Foundation, Swedish Medical Society, Gothenburg Medical Society, the Swedish Society for Medical Research, SWEGENE Center for Bio-Imaging (CBI) at Gothenburg University, and the UK Medical Research Council (G9802186).

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Correspondence to John-Olov Jansson.

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Wallenius, V., Wallenius, K., Ahrén, B. et al. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8, 75–79 (2002). https://doi.org/10.1038/nm0102-75

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