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.
| Original language | English |
|---|---|
| Pages (from-to) | 1456-1465 |
| Number of pages | 10 |
| Journal | Diabetologia |
| Volume | 57 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jan 1 2014 |
| Externally published | Yes |
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Keywords
- Adipokines
- Adipose tissue inflammation
- CXCL12
- Macrophage recruitment
- SDF1
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
CXCL12 secreted from adipose tissue recruits macrophages and induces insulin resistance in mice. / Kim, Dayea; Kim, Jaeyoon; Yoon, Jong Hyuk; Ghim, Jaewang; Yea, Kyungmoo; Song, Parkyong; Park, Soyeon; Lee, Areum; Hong, Chun Pyo; Jang, Min Seong; Kwon, Yonghoon; Park, Sehoon; Jang, Myoung Ho; Berggren, Per Olof; Suh, Pann Ghill; Ryu, Sung Ho.
In: Diabetologia, Vol. 57, No. 7, 01.01.2014, p. 1456-1465.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CXCL12 secreted from adipose tissue recruits macrophages and induces insulin resistance in mice
AU - Kim, Dayea
AU - Kim, Jaeyoon
AU - Yoon, Jong Hyuk
AU - Ghim, Jaewang
AU - Yea, Kyungmoo
AU - Song, Parkyong
AU - Park, Soyeon
AU - Lee, Areum
AU - Hong, Chun Pyo
AU - Jang, Min Seong
AU - Kwon, Yonghoon
AU - Park, Sehoon
AU - Jang, Myoung Ho
AU - Berggren, Per Olof
AU - Suh, Pann Ghill
AU - Ryu, Sung Ho
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - Adipokines
KW - Adipose tissue inflammation
KW - CXCL12
KW - Macrophage recruitment
KW - SDF1
UR - http://www.scopus.com/inward/record.url?scp=84903531205&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84903531205&partnerID=8YFLogxK
U2 - 10.1007/s00125-014-3237-5
DO - 10.1007/s00125-014-3237-5
M3 - Article
VL - 57
SP - 1456
EP - 1465
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 7
ER -