RT Journal Article
SR Electronic
T1 Adipose Tissue Exosome-Like Vesicles Mediate Activation of Macrophage-Induced Insulin Resistance
JF Diabetes
JO Diabetes
FD American Diabetes Association
SP 2498
OP 2505
DO 10.2337/db09-0216
VO 58
IS 11
A1 Deng, Zhong-bin
A1 Poliakov, Anton
A1 Hardy, Robert W.
A1 Clements, Ronald
A1 Liu, Cunren
A1 Liu, Yuelong
A1 Wang, Jianhua
A1 Xiang, Xiaoyu
A1 Zhang, Shuangqin
A1 Zhuang, Xiaoying
A1 Shah, Spandan V.
A1 Sun, Dongmei
A1 Michalek, Sue
A1 Grizzle, William E.
A1 Garvey, Timothy
A1 Mobley, Jim
A1 Zhang, Huang-Ge
YR 2009
UL http://diabetes.diabetesjournals.org/content/58/11/2498.abstract
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