Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance.
Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance.
复制标题
脂肪组织外泌体样囊泡介导巨噬细胞诱导的胰岛素抵抗的激活。
作者：
Deng ZB;Poliakov A;Hardy RW;Clements R;Liu C;Liu Y;Wang J;Xiang X;Zhang S;Zhuang X;Shah SV;Sun D;Michalek S;Grizzle WE;Garvey T;Mobley J;Zhang HG
在小鼠模型中，我们试图确定脂肪组织释放的外泌体样囊泡（ELVs）是否在巨噬细胞的激活和随后的胰岛素抵抗发展中发挥作用。通过蔗糖梯度离心纯化脂肪组织中释放的ELVs，用绿色荧光染料标记，然后静脉注射到B6 ob/ob小鼠（肥胖模型）或B6高脂小鼠。通过荧光活化细胞分选仪分析活化标记物和ELISA诱导炎性细胞因子检测注射ELVs对巨噬细胞活化的影响。葡萄糖耐量和胰岛素耐量也进行了评估。同样，用敲除TLR2、TLR4、MyD88和含有toll -白细胞介素-1受体（TIR）结构域的接头蛋白诱导干扰素-β (TRIF)的不同基因的B6小鼠，测试它们对注射elv的反应。elv被外周血单核细胞吸收，然后分化为活化的巨噬细胞，并增加肿瘤坏死因子-α (TNF-α)和白细胞介素-6 （IL-6）的分泌。向野生型C57BL/6小鼠注射obELVs可导致胰岛素抵抗的发生。当将obELVs静脉注射到TLR4基因敲除的B6小鼠体内时，葡萄糖耐受不良和胰岛素抵抗的水平明显降低。RBP4在obelv中富集。重组RBP4预孵育的骨髓源性巨噬细胞导致obelv介导的IL-6和TNF-α的诱导减弱。脂肪组织释放的elv可以作为脂肪组织和巨噬细胞之间的一种通讯模式。obelv介导的巨噬细胞TNF-α和IL-6的诱导和胰岛素抵抗需要TLR4/TRIF通路。
We sought to determine whether exosome-like vesicles (ELVs) released from adipose tissue play a role in activation of macrophages and subsequent development of insulin resistance in a mouse model. ELVs released from adipose tissue were purified by sucrose gradient centrifugation and labeled with green fluorescent dye and then intravenously injected into B6 ob/ob mice (obese model) or B6 mice fed a high-fat diet. The effects of injected ELVs on the activation of macrophages were determined through analysis of activation markers by fluorescence-activated cell sorter and induction of inflammatory cytokines using an ELISA. Glucose tolerance and insulin tolerance were also evaluated. Similarly, B6 mice with different gene knockouts including TLR2, TLR4, MyD88, and Toll-interleukin-1 receptor (TIR) domain–containing adaptor protein inducing interferon-β (TRIF) were also used for testing their responses to the injected ELVs. ELVs are taken up by peripheral blood monocytes, which then differentiate into activated macrophages with increased secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Injection of obELVs into wild-type C57BL/6 mice results in the development of insulin resistance. When the obELVs were intravenously injected into TLR4 knockout B6 mice, the levels of glucose intolerance and insulin resistance were much lower. RBP4 is enriched in the obELVs. Bone marrow–derived macrophages preincubated with recombinant RBP4 led to attenuation of obELV-mediated induction of IL-6 and TNF-α. ELVs released by adipose tissue can act as a mode of communication between adipose tissues and macrophages. The obELV-mediated induction of TNF-α and IL-6 in macrophages and insulin resistance requires the TLR4/TRIF pathway.
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影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
DOI：
10.1016/j.bbrc.2008.11.050
发表时间：
2009-01-16
影响因子：
3.1
作者：
Looze, Christopher;Yui, David;Leung, Lester;Ingham, Matthew;Kaler, Maryann;Yao, Xianglan;Wu, Wells W.;Shen, Rong-Fong;Daniels, Mathew P.;Levine, Stewart J.
通讯作者：
Levine, Stewart J.
影响因子：
4.8
作者：
HOFMANN, C;LORENZ, K;SPIEGELMAN, BM
通讯作者：
SPIEGELMAN, BM
影响因子：
7.7
作者：
Nakamachi, Takafumi;Nomiyama, Takashi;Bruemmer, Dennis
通讯作者：
Bruemmer, Dennis
影响因子：
158.5
作者：
Graham, Timothy E.;Yang, Qin;Kahn, Barbara B.
通讯作者：
Kahn, Barbara B.