Visceral Adipose Tissue Derived Exosomes Exacerbate Colitis Severity <i>via</i> Pro-inflammatory MiRNAs in High Fat Diet Fed Mice

Abstract

A pioneering epidemic study has revealed a strong association between obesity and the risk of colitis. In this study, a high fat diet was found to significantly aggravate colitis induced by dextran sulfate sodium (DSS). Meanwhile, a high fat diet changed the miRNA profile of the visceral adipose exosomes, switching the exosomes from anti-inflammatory to a pro-inflammatory phenotype. Strikingly, these inflammatory exosomes efficiently circulated into the <i>lamina propria</i> of the intestine, while these exosomes predisposed the intestine to inflammation <i>via</i> promoting macrophage M1 polarization. Mechanistically, the exosomes promoted M1 differentiation at least partially <i>via</i> transferring pro-inflammatory miRNAs, such as miR-155. Moreover, exosome-mediated miR-155 inhibitor delivery significantly prevented DSS-induced colitis. Together, the study has revealed an exosomal pathway of how obesity aggravates colitis and proposes an exosome-based intervention strategy for colitis management.