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
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyeongbuk, 790-784, Republic of Korea.
Diabetologia. 2014 Jul;57(7):1456-65. doi: 10.1007/s00125-014-3237-5. Epub 2014 Apr 18.
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.
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.
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.
目的/假设：肥胖诱导的炎症是由巨噬细胞募集到脂肪组织引发的。这些被募集的巨噬细胞称为脂肪组织巨噬细胞，它们分泌多种促炎细胞因子，导致低度全身炎症和胰岛素抵抗。本研究的目的是寻找巨噬细胞募集因子，这些因子被认为在肥胖和胰岛素抵抗之间提供了关键联系。
我们使用趋化性分析、反相高效液相色谱和串联质谱分析从脂肪细胞中寻找趋化因子。通过定量逆转录聚合酶链反应、免疫组织化学和流式细胞术分析评估趋化因子和巨噬细胞标志物的表达。
我们报告了从3T3-L1脂肪细胞条件培养基中鉴定出趋化因子（C-X-C基序）配体12（CXCL12，也称为基质细胞衍生因子1），它通过其受体趋化因子（C-X-C基序）受体4（CXCR4）诱导单核细胞迁移。饮食诱导的肥胖小鼠白色脂肪组织中CXCL12表达显著增加。用CXCR4拮抗剂治疗肥胖小鼠可减少白色脂肪组织中巨噬细胞的积累和促炎细胞因子的产生，并改善全身胰岛素敏感性。
结论/解读：在本研究中，我们发现CXCL12是一种脂肪细胞衍生的趋化因子，可募集巨噬细胞，并且它是肥胖诱导的脂肪组织炎症和全身胰岛素抵抗形成所必需的因子。
