The inflammasome is a central player in the induction of obesity and insulin resistance

  • Rinke Stienstra (Creator)
  • Janna A. Van Diepen (Creator)
  • Cees J. Tack (Creator)
  • Mohammad H. Zaki (Creator)
  • Frank L. van de Veerdonk (Creator)
  • Deshani Perera (Creator)
  • Geoff Neal (Creator)
  • Anneke Hijmans (Creator)
  • Irene O. Vroegrijk (Creator)
  • Sjoerd A. van den Berg (Creator)
  • Johannes A. Romijn (Creator)
  • Patrick C. Rensen (Creator)
  • Leo A. Joosten (Creator)
  • Mihai G. Netea (Creator)
  • Thirumala-Devi D. Kanneganti (Creator)



Inflammation plays a key role in the pathogenesis of obesity. Chronic overfeeding leads to macrophage infiltration in the adipose tissue, resulting in pro-inflammatory cytokine production. Both microbial and endogenous danger signals trigger assembly of the intracellular innate immune sensor Nlrp3 [NLR family, pyrin domain containing 3] resulting in caspase-1 activation and production of pro-inflammatory cytokines interleukin (IL)-1beta and IL-18. Here, we showed that mice deficient in Nlrp3, ASC [apoptosis-associated speck-like protein containing a CARD; a.k.a PYCARD (PYD and CARD domain containing)] and caspase-1 were resistant to the development of high fat diet-induced obesity, which correlated with protection from obesity-induced insulin resistance. Detailed metabolic and molecular phenotyping demonstrated that the inflammasome controls energy expenditure and adipogenic gene expression during chronic overfeeding. These findings reveal a critical function of the inflammasome in obesity and insulin resistance and suggest inhibition of the inflammasome as a potential therapeutic strategy.
Date made available21 Aug 2011
PublisherWageningen University

Research Output

Inflammasome is a central player in the induction of obesity and insulin resistance

Stienstra, R., van Diepen, J. A., Tack, C. J., Zaki, M. H., van de Veerdonk, F. L., Perera, D., Neale, G. A., Hooiveld, G. J. E. J., Hijmans, A., Vroegrijk, I., Berg, S., Romijn, J., Rensen, P. C. N., Joosten, L. A. B., Netea, M. G. & Kanneganti, T. D., 2011, In : Proceedings of the National Academy of Sciences of the United States of America. 108, 37, p. 15324-15329

Research output: Contribution to journalArticleAcademicpeer-review

Open Access
  • 393 Citations (Scopus)

    Cite this

    Stienstra, R. (Creator), van Diepen, J. A. (Creator), Tack, C. J. (Creator), Zaki, M. H. (Creator), van de Veerdonk, F. L. (Creator), Perera, D. (Creator), Neal, G. (Creator), Hijmans, A. (Creator), Vroegrijk, I. O. (Creator), van den Berg, S. A. (Creator), Romijn, J. A. (Creator), Rensen, P. C. (Creator), Joosten, L. A. (Creator), Netea, M. G. (Creator), Kanneganti, T. D. (Creator) (21 Aug 2011). The inflammasome is a central player in the induction of obesity and insulin resistance. Wageningen University.