"Circulating exosome-like vesicles of humans with nondiabetic obesity impaired islet beta-cell proliferation, which was associated with decreased Omentin-1 protein cargo"

作者全名："Ge, Qian; Xie, Xinxin; Chen, Xiangjun; Huang, Rongfeng; Rui, Cheng-Xue; Zhen, Qianna; Hu, Renzhi; Wu, Min; Xiao, Xiaoqiu; Li, Xi"

作者地址："[Ge, Qian; Chen, Xiangjun; Zhen, Qianna; Hu, Renzhi] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrinol, Chongqing 400016, Peoples R China; [Xie, Xinxin; Rui, Cheng-Xue; Li, Xi] Chongqing Med Univ, Biol Sci Inst, Chongqing 400016, Peoples R China; [Huang, Rongfeng; Wu, Min; Xiao, Xiaoqiu] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Translat Med Major Metab Dis, Chongqing 400016, Peoples R China; [Rui, Cheng-Xue] Catholic Univ Louvain, Duve Inst, B-1200 Brussels, Belgium; [Xiao, Xiaoqiu] Yixueyuan Rd, Yuzhong Dist, Chongqing 400016, Peoples R China; [Li, Xi] Friendship Rd, Yuzhong Dist, Chongqing 400016, Peoples R China"

通信作者："Xiao, XQ (通讯作者)，Yixueyuan Rd, Yuzhong Dist, Chongqing 400016, Peoples R China.; Li, X (通讯作者)，Friendship Rd, Yuzhong Dist, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000811186800004

JCR分区：Q1

影响因子：6.8

年份：2022

卷号：9

期号：4

开始页：1099

结束页：1113

文献类型：Article

关键词：beta-Cell; Exosome; Obesity; Proliferation; Type 2 diabetes mellitus

摘要："The regulation of beta-cell mass in the status of nondiabetic obesity remains not well understood. We aimed to investigate the role of circulating exosome-like vesicles (ELVs) isolated from humans with simple obesity in the regulation of islet beta-cell mass. Between June 2017 and July 2019, 81 subjects with simple obesity and 102 healthy volunteers with normal weight were recruited. ELVs were isolated by ultra-centrifugation. The proliferations of beta-cells and islets were measured by 5-ethynl-20-deoxyuridine (EdU). Protein components in ELVs were identified by Quantitative Proteomic Analysis and verified by Western blot and ELISA. The role of specific exosomal protein was analyzed by gain-of-function approach in ELVs released by 3T3-L1 preadipocytes. Circulating ELVs from subjects with simple obesity inhibited beta-cell proliferation in vitro without affecting its apoptosis, secretion, and inflammation. The protein levels of Rictor and Omentin-1 were downregulated in circulating ELVs from subjects with simple obesity and associated with the obesity-linked pathologic conditions. The ELV-carried Omentin-1 and Omentin-1 protein per se were validated to increase beta-cell proliferation and activate Akt signaling pathway. Moreover, Omentin-1 in ELVs was downregulated by insulin. The circulating ELVs may act as a negative regulator for beta-cell mass in nondiabetic obesity through inhibiting beta-cell proliferation. This effect was associated with downregulated Omentin-1 protein in ELVs. This newly identified ELV-carried protein could be a mediator linking insulin resistance to impaired beta-cell proliferation and a new potential target for increasing beta-cell mass in obesity and T2DM. Copyright (C) 2021, Chongqing Medical University. Production and hosting by Elsevier B.V."

基金机构："National Key R&D Program of China [2018YFA0800401]; National Natural Science Foundation of China [81200629, 81570763, 81770861, 31571401]; Fundamental Science and Advanced Technology Research of Chongqing [CSTC2015jcyjB0146]; Chongqing Science and Technology Foundation [cstc2018jcyjAX0232]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJZD-K201800402]"

基金资助正文："This work was supported by the National Key R&D Program of China (No. 2018YFA0800401); the National Natural Science Foundation of China (No. 81200629, 81570763, 81770861 and 31571401); the Fundamental Science and Advanced Technology Research of Chongqing (Major Project, No. CSTC2015jcyjB0146); the Chongqing Science and Technology Foundation (No. cstc2018jcyjAX0232); the Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJZD-K201800402)."