Adipose tissue IL-18 production is independent of caspase-1 and caspase-11

Abstract

Abstract Inflammation in the adipose tissue resulting from imbalanced caloric intake and energy expenditures promotes the metabolic alteration observed in obesity. This inflammatory process is initiated by the production of inflammatory cytokines like IL-1b and IL-18. Opposing functions for these cytokines on the metabolism have been documented. While IL-1b promotes insulin resistance and diabetes, IL-18 promotes energy expenditures and regulates food intake. The production of IL-1b and IL-18 in the adipose tissue of obese mice was thought to be mediated by caspase-1 upon activation of the Nlrp3 inflammasome in response to lipid excess, and by the Nlrp1b inflammasome activation in response to energy excess, respectively. However, this is not the case, here we show that IL-18 production in the adipose tissue is independent of caspase-1 activity. Together, our results indicate that in response to metabolic stress signals IL-18 production is mediated by the Nlrp1b inflammasome in a caspase-1-independent manner while the Nlrp3-mediated IL-1b production is caspase-1 dependent.