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, Soo Hyun Kim, Hadar Eini, Eli C. Lewis, Leo A.B. Joosten, Herbert Tilg, Mihai G. Netea, Cees J. Tack, Charles A. DinarelloRinke Stienstra

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

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.

Original languageEnglish
Article number4711
JournalNature Communications
Volume5
DOIs
StatePublished - 3 Sep 2014

ASJC Scopus subject areas

  • Chemistry (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Physics and Astronomy (all)

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