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IL-37 protects against obesity-induced inflammation and insulin resistance

Author

Listed:
  • Dov B. Ballak

    (Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands)

  • Janna A. van Diepen

    (Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands)

  • Alexander R. Moschen

    (Children’s Hospital, Ludwig-Maximilians University)

  • Henry J. Jansen

    (Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands)

  • Anneke Hijmans

    (Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands)

  • Gert-Jan Groenhof

    (Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands)

  • Floris Leenders

    (Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands)

  • Philip Bufler

    (Children’s Hospital, Ludwig-Maximilians University)

  • Mark V. Boekschoten

    (Wageningen University)

  • Michael Müller

    (Wageningen University)

  • Sander Kersten

    (Wageningen University)

  • Suzhao Li

    (University of Colorado Denver)

  • SooHyun Kim

    (Konkuk University)

  • Hadar Eini

    (Ben-Gurion University of the Negev)

  • Eli C. Lewis

    (Ben-Gurion University of the Negev)

  • Leo A. B. Joosten

    (Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands)

  • Herbert Tilg

    (Christian Doppler Research Laboratory for Gut Inflammation, Medical University Innsbruck)

  • Mihai G. Netea

    (Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands)

  • Cees J. Tack

    (Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands)

  • Charles A. Dinarello

    (Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands
    University of Colorado Denver)

  • Rinke Stienstra

    (Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands
    Wageningen University)

Abstract

Cytokines of the IL-1 family are important modulators of obesity-induced inflammation and the development of systemic insulin resistance. Here we show that IL-1 family member IL-37, recently characterized as an anti-inflammatory cytokine, ameliorates obesity-induced inflammation and insulin resistance. Mice transgenic for human IL-37 (IL-37tg) exhibit reduced numbers of adipose tissue macrophages, increased circulating levels of adiponectin and preserved glucose tolerance and insulin sensitivity after 16 weeks of HFD. In vitro treatment of adipocytes with recombinant IL-37 reduces adipogenesis and activates AMPK signalling. In humans, elevated steady-state IL-37 adipose tissue mRNA levels are positively correlated with insulin sensitivity and a lower inflammatory status of the adipose tissue. These findings reveal IL-37 as an important anti-inflammatory modulator during obesity-induced inflammation and insulin resistance in both mice and humans, and suggest that IL-37 is a potential target for the treatment of obesity-induced insulin resistance and type 2 diabetes.

Suggested Citation

  • Dov B. Ballak & Janna A. van Diepen & Alexander R. Moschen & Henry J. Jansen & Anneke Hijmans & Gert-Jan Groenhof & Floris Leenders & Philip Bufler & Mark V. Boekschoten & Michael Müller & Sander Kers, 2014. "IL-37 protects against obesity-induced inflammation and insulin resistance," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5711
    DOI: 10.1038/ncomms5711
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