RGD Reference Report - Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. - Rat Genome Database

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Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance.

Authors: 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 
Citation: Deng ZB, etal., Diabetes. 2009 Aug 12.
RGD ID: 2312483
Pubmed: PMID:19675137   (View Abstract at PubMed)
PMCID: PMC2768161   (View Article at PubMed Central)
DOI: DOI:10.2337/db09-0216   (Journal Full-text)

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 FACS 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 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 TNF-alpha and 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 (BMDM) pre-incubated with recombinant RBP4 led to attenuation of obELV-mediated induction of IL-6 and TNF-alpha. Conclusions- ELVs released by adipose tissue can act as a mode of communication between adipose tissues and macrophages. The obELV mediated induction of TNF-alpha and IL-6 in macrophages and insulin resistance requires the TLR4/TRIF pathway.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Insulin Resistance  ISOTlr4 (Mus musculus)2312483; 2312483associated with ObesityRGD 
Insulin Resistance  IAGP 2312483associated with ObesityRGD 

Objects Annotated

Genes (Rattus norvegicus)
Tlr4  (toll-like receptor 4)

Genes (Mus musculus)
Tlr4  (toll-like receptor 4)

Genes (Homo sapiens)
TLR4  (toll like receptor 4)


Additional Information