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

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 Kersten, Suzhao Li, SooHyun Kim, Hadar Eini, Eli C. Lewis, Leo A. B. Joosten, Herbert Tilg, Mihai G. Netea, Cees J. Tack, Charles A. Dinarello and Rinke Stienstra ()
Additional contact information
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
Rinke Stienstra: Radboud University Medical Centre, Geert Grooteplein 8, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5711

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