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

作者：Mengying Wei, Xiaotong Gao, Lijun Liu, Zhelong Li, Zhuo Wan, Yan Dong, Xutao Chen, Yu Zhe Niu, Jian Zhang, Guodong Yang · 发表于：ACS Nano · 年份：2020 · DOI：10.1021/acsnano.0c01860 · 被引用次数：152 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Circular RNAs in diseases

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 lamina propria of the 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 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.