Impact of caspase‐11 non‐canonical inflammasome on adipose tissue inflammation and obesity induced insulin resistance

Abstract

Sterile inflammation in the absence of overt infection contributes to insulin‐resistance and type 2 diabetes. IL‐1β mediates sustained tissue damage during the development of type 2 diabetes and is controlled by caspase‐1. Caspase‐1 is activated by multiple inflammasome protein complexes. We have shown that canonical Nlrp3 inflammasome activation participates in high‐fat diet induced adipose tissue inflammation and insulin‐resistance. Caspase‐11 has recently been identified as a non‐canonical inflammasome that leads to caspase‐1 activation in response to gram‐negative bacteria. Intestinal barrier function may be impaired during obesity and diabetes, making caspase‐11 a potential mediator of chronic inflammation during these diseases. Therefore we tested the hypothesis that caspase‐11 contributes to inflammasome activation, IL‐1β production and adipose tissue lymphocytosis during obesity. Our findings suggest that that high‐fat fed caspase‐11 −/− mice are not protected from lymphocytosis, adipose tissue inflammation and glucose and insulin intolerance. These data suggest that the caspase‐11 non‐canonical inflammasome is not the major innate immune sensor of obesity‐associated changes in endogenous gut microbial species that drive inflammation and insulin‐resistance. This research was supported in part by NIH DK090556, and RWG is supported by NIH DK064584.