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Diabetologia
Published in: Diabetologia 7/2014

01-07-2014 | Article

CXCL12 secreted from adipose tissue recruits macrophages and induces insulin resistance in mice

Authors: Dayea Kim, Jaeyoon Kim, Jong Hyuk Yoon, Jaewang Ghim, Kyungmoo Yea, Parkyong Song, Soyeon Park, Areum Lee, Chun-Pyo Hong, Min Seong Jang, Yonghoon Kwon, Sehoon Park, Myoung Ho Jang, Per-Olof Berggren, Pann-Ghill Suh, Sung Ho Ryu

Published in: Diabetologia | Issue 7/2014

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Abstract

Aims/hypothesis

Obesity-induced inflammation is initiated by the recruitment of macrophages into adipose tissue. The recruited macrophages, called adipose tissue macrophages, secrete several proinflammatory cytokines that cause low-grade systemic inflammation and insulin resistance. The aim of this study was to find macrophage-recruiting factors that are thought to provide a crucial connection between obesity and insulin resistance.

Methods

We used chemotaxis assay, reverse phase HPLC and tandem MS analysis to find chemotactic factors from adipocytes. The expression of chemokines and macrophage markers was evaluated by quantitative RT-PCR, immunohistochemistry and FACS analysis.

Results

We report our finding that the chemokine (C-X-C motif) ligand 12 (CXCL12, also known as stromal cell-derived factor 1), identified from 3T3-L1 adipocyte conditioned medium, induces monocyte migration via its receptor chemokine (C-X-C motif) receptor 4 (CXCR4). Diet-induced obese mice demonstrated a robust increase of CXCL12 expression in white adipose tissue (WAT). Treatment of obese mice with a CXCR4 antagonist reduced macrophage accumulation and production of proinflammatory cytokines in WAT, and improved systemic insulin sensitivity.

Conclusions/interpretation

In this study we found that CXCL12 is an adipocyte-derived chemotactic factor that recruits macrophages, and that it is a required factor for the establishment of obesity-induced adipose tissue inflammation and systemic insulin resistance.
Appendix
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Metadata
Title
CXCL12 secreted from adipose tissue recruits macrophages and induces insulin resistance in mice
Authors
Dayea Kim
Jaeyoon Kim
Jong Hyuk Yoon
Jaewang Ghim
Kyungmoo Yea
Parkyong Song
Soyeon Park
Areum Lee
Chun-Pyo Hong
Min Seong Jang
Yonghoon Kwon
Sehoon Park
Myoung Ho Jang
Per-Olof Berggren
Pann-Ghill Suh
Sung Ho Ryu
Publication date
01-07-2014
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 7/2014
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-014-3237-5

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