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

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

doi:10.1007/s00125-014-3237-5

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

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

Department of New Biology

Research output: Contribution to journal › Article › peer-review

124 Scopus citations

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	https://doi.org/10.1007/s00125-014-3237-5
State	Published - Jul 2014

Bibliographical note

Funding Information:
Funding This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2013R1A2A1A03010110 and No.2010-0028684). This work was also funded by the GyeongSangBuk-Do Forestry Environment Research Institute.

Keywords

Adipokines
Adipose tissue inflammation
CXCL12
Macrophage recruitment
SDF1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00125-014-3237-5

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@article{10138f6d09aa4d21803a00535a88f14f,

title = "CXCL12 secreted from adipose tissue recruits macrophages and induces insulin resistance in mice",

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.",

keywords = "Adipokines, Adipose tissue inflammation, CXCL12, Macrophage recruitment, SDF1",

author = "Dayea Kim and Jaeyoon Kim and Yoon, \{Jong Hyuk\} and Jaewang Ghim and Kyungmoo Yea and Parkyong Song and Soyeon Park and Areum Lee and Hong, \{Chun Pyo\} and Jang, \{Min Seong\} and Yonghoon Kwon and Sehoon Park and Jang, \{Myoung Ho\} and Berggren, \{Per Olof\} and Suh, \{Pann Ghill\} and Ryu, \{Sung Ho\}",

note = "Funding Information: Funding This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2013R1A2A1A03010110 and No.2010-0028684). This work was also funded by the GyeongSangBuk-Do Forestry Environment Research Institute.",

year = "2014",

month = jul,

doi = "10.1007/s00125-014-3237-5",

language = "English",

volume = "57",

pages = "1456--1465",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "7",

}

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

N1 - Funding Information: Funding This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (No. 2013R1A2A1A03010110 and No.2010-0028684). This work was also funded by the GyeongSangBuk-Do Forestry Environment Research Institute.

PY - 2014/7

Y1 - 2014/7

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 - https://www.scopus.com/pages/publications/84903531205

U2 - 10.1007/s00125-014-3237-5

DO - 10.1007/s00125-014-3237-5

M3 - Article

C2 - 24744121

AN - SCOPUS:84903531205

SN - 0012-186X

VL - 57

SP - 1456

EP - 1465

JO - Diabetologia

JF - Diabetologia

IS - 7

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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