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

Raiza R. BonomoiD, Sarah Talley, Jomana HatahetiD, Chaitanya K. GaviniiD, Tyler M. CookiD, Ben Chun, Peter Michael Kekenes-HuskeyiD, Grégory AubertiD, Edward M. CampbelliD, Virginie Mansuy‐AubertiD

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.

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02 /Specification & Classification

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