Visceral Adipose Tissue Derived Exosomes Exacerbate Colitis Severity via Pro-inflammatory MiRNAs in High Fat Diet Fed Mice
Visceral Adipose Tissue Derived Exosomes Exacerbate Colitis Severity via Pro-inflammatory MiRNAs in High Fat Diet Fed Mice
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DOI：
10.1021/acsnano.0c01860
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发表时间：
2020-04-28
期刊：
影响因子：
17.1
通讯作者：
Yang, Guodong
中科院分区：
文献类型：
--
作者：
Wei, Mengying;Gao, Xiaotong;Yang, Guodong
一项开创性的流行病学研究揭示了肥胖与结肠炎风险之间的密切联系。在这项研究中，发现高脂肪饮食显著加重葡聚糖硫酸钠（DSS）诱导的结肠炎。同时，高脂肪饮食改变了内脏脂肪外泌体的miRNA谱，将外泌体从抗炎表型转变为促炎表型。引人注目的是，这些炎性外泌体有效地循环到肠的固有层中，而这些外泌体通过促进巨噬细胞M1极化使肠易于炎症。从机制上讲，外泌体至少部分通过转移促炎性miRNA（如miR-155）促进M1分化。此外，外泌体介导的miR-155抑制剂递送显著预防DSS诱导的结肠炎。总之，这项研究揭示了肥胖如何使结肠炎恶化的外泌体途径，并提出了一种基于外泌体的结肠炎管理干预策略。
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 proinflammatory phenotype. Strikingly, these inflammatory exosomes eff iciently 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.