Visceral Adipose Tissue Derived Exosomes Exacerbate Colitis Severity via Pro-Inflammatory MiRNAs in High Fat Diet Fed Mice.

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