Live Monitoring of Inflammation Reveals Tissue and Sex-specific Responses to Western Diet and Butyrate treatment

Abstract

Obesity is a current epidemic, affecting millions of individuals worldwide. Chronic obesity is characterized by a low grade systemic inflammation besides not being a classic inflammatory disease. Many studies have tried to identify inflammatory insults dysregulated by a Westernized diet consisted of high fat, high sucrose, and high cholesterol mainly focusing on production and secretion of inflammatory cytokines. The gut microbiome and derived metabolites, including the short-chain fatty acid butyrate, have received increased attention as underlying some of the obesogenic features. In the present work, we utilized a novel biosensor mouse model capable of monitoring in vivo inflammation. We observed tissue- and sex- specific caspase 1 activation patterns in obese mice and treated with butyrate. Our work utilizing a caspase-1 biosensor mouse model, flow cytometry and computational analyses and offers new mechanistic insights underlying the effect of butyrate in obesity and its complications.

Characterization of age-associated inflammasome activation reveals tissue specific differences in transcriptional and post-translational inflammatory responses

“…To characterize global and tissue-specific changes in inflammasome activation during the process of aging, we utilized a transgenic mouse model in which a luciferase-based caspase-1 biosensor is constitively expressed in all tissues (37). Proteolytic activation of caspase-1 thus induces luciferase activation in specific tissues, allowing inflammasome activation to be monitored in vivo and ex vivo (37)(38)(39)(40)(41)(42)(43). These studies reveal a tissue-specific degree of overlap or discordance between age-associated inflammasome activation and upregulation of inflammatory transcripts commonly associated with inflammaging.…”