title: CXCL12 secreted from adipose tissue recruits macrophages and induces insulin resistance in mice.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, 790-784, Republic of Korea.
authors.forename: Dayea
authors.initials: D
authors.lastname: Kim
authors.forename: Jaeyoon
authors.initials: J
authors.lastname: Kim
authors.forename: Jong Hyuk
authors.initials: JH
authors.lastname: Yoon
authors.forename: Jaewang
authors.initials: J
authors.lastname: Ghim
authors.forename: Kyungmoo
authors.initials: K
authors.lastname: Yea
authors.forename: Parkyong
authors.initials: P
authors.lastname: Song
authors.forename: Soyeon
authors.initials: S
authors.lastname: Park
authors.forename: Areum
authors.initials: A
authors.lastname: Lee
authors.forename: Chun-Pyo
authors.initials: CP
authors.lastname: Hong
authors.forename: Min Seong
authors.initials: MS
authors.lastname: Jang
authors.forename: Yonghoon
authors.initials: Y
authors.lastname: Kwon
authors.forename: Sehoon
authors.initials: S
authors.lastname: Park
authors.forename: Myoung Ho
authors.initials: MH
authors.lastname: Jang
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.forename: Pann-Ghill
authors.initials: PG
authors.lastname: Suh
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: Ryu
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009765:Obesity / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12
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