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)

Dataset

Description

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

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