PT  - JOURNAL ARTICLE
AU  - Deng, Zhong-bin
AU  - Poliakov, Anton
AU  - Hardy, Robert W.
AU  - Clements, Ronald
AU  - Liu, Cunren
AU  - Liu, Yuelong
AU  - Wang, Jianhua
AU  - Xiang, Xiaoyu
AU  - Zhang, Shuangqin
AU  - Zhuang, Xiaoying
AU  - Shah, Spandan V.
AU  - Sun, Dongmei
AU  - Michalek, Sue
AU  - Grizzle, William E.
AU  - Garvey, Timothy
AU  - Mobley, Jim
AU  - Zhang, Huang-Ge
TI  - Adipose Tissue Exosome-Like Vesicles Mediate Activation of Macrophage-Induced Insulin Resistance
AID  - 10.2337/db09-0216
DP  - 2009 Nov 01
TA  - Diabetes
PG  - 2498--2505
VI  - 58
IP  - 11
4099  - http://diabetes.diabetesjournals.org/content/58/11/2498.short
4100  - http://diabetes.diabetesjournals.org/content/58/11/2498.full
SO  - Diabetes2009 Nov 01; 58
AB  - OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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. RESULTS 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. CONCLUSIONS 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. © 2009 American Diabetes Association