Adipocyte-derived microvesicles from obese mice induce M1 macrophage phenotype through secreted miR-155  

作　　者：Yaqin Zhang Hongliang Mei Xiaoai Chang Fang Chen Yunxia Zhu Xiao Han 

机构地区：[1]Key Laboratory of Human Functional Genomics of Jiangsu Province,Department of Biochemistry and Molecular Biology,Nanjing Medical University,140 Hanzhong Road,Nanjing 210029,China

出　　处：《Journal of Molecular Cell Biology》2016年第6期505-517,共13页分子细胞生物学报（英文版）

基　　金：supported by research grants from the Ministry of Science and Technology(2012CB524900);the National Natural Science Foundation of China(81400787);the Natural Science Foundation of Jiangsu Province,China(BK20130890);the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(13KJB320013);the Specialized Research Fund for the Doctoral Program of Higher Education,China(20133234120006).

摘　　要：The pro-inflammatory profile of M1 macrophage accumulation in adipose tissue is a central event leading to the metabolic complications of obesity.However,the mechanisms by which M1 macrophages are enriched in adipose tissue during weight gain remain incompletely understood.Here,we investigated the effects of adipocyte-derived microvesicles(ADM)on modulating macrophage phenotype in mice and explored the involved molecular signalling pathways.We found that,compared with ADM from lean mice(SD ADM),ADM from obese mice(HFD ADM)significantly enhanced M1 marker expression.The quantitative RTPCR assay demonstrated that miR-155 was upregulated in both HFD ADM and HFD ADM-treated macrophages.By depleting miR-155 expression in HFD ADM and increasing miR-155 level in SD ADM,we further illustrated that miR-155 in ADM-induced M1 macrophage polarization.Functionally,in contrast to SD ADM,HFD ADM significantly decreased the protein level of SOCS1,a proven miR-155 target,leading to activation of STAT1,and suppression of STAT6 signalling;these effects were reversed by silencing miR-155 in HFD ADM.Furthermore,the supernatant of bone marrow-derived macrophages pre-stimulated with miR-155-bearing ADM interfered with insulin signalling and insulin-induced glucose uptake in adipocytes.Collectively,these results provide the first evidence that M1 macrophage polarization can be mediated by miR-155-bearing ADM,which reciprocally regulates insulin signalling and glucose uptake in adipocytes.Our study reveals a novel mechanism through which obesity induces an imbalance in the M1-to-M2 macrophage ratio in adipose tissue,thus causing chronic inflammation and local insulin resistance.

关 键 词：ADIPOCYTE MACROPHAGE PHENOTYPE MICROVESICLE MIR-155 

分 类 号：R73[医药卫生—肿瘤]