CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity

CC chemokine and CC chemokine receptor profiles in visceral and subcutaneous adipose tissue are altered in human obesity
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DOI:
10.1210/jc.2007-2630
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发表时间:
2008-08-01
影响因子:
5.8
通讯作者:
Stulnig, Thomas M.
Stulnig, Thomas M.
中科院分区:
医学2区
文献类型:
--
作者:
Huber, Joakim;Kiefer, Florian W.;Stulnig, Thomas M.

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背景/目的:肥胖与低度炎症、胰岛素抵抗和脂肪组织巨噬细胞浸润有关。CC趋化因子及其各自的受体在人类脂肪组织炎症中的作用仍有待确定。方法:肥胖患者sc和内脏脂肪组织(体重指数53.1 +/-11.3 kg/m2)与瘦对照组相比(体重指数25.9 +/-3.8 kg/m2)分析炎症基因表达的改变。通过巨噬细胞特异性标志物(CD68)mRNA表达的增加和巨噬细胞浸润的升高,确定肥胖患者皮下和内脏脂肪组织中巨噬细胞浸润增加。参与单核细胞趋化的CC趋化因子(CCL2、CCL3、CCL5、CCL7、CCL8和CCL11)及其受体(CCR1、CCR2、CCR3和CCR5)的基因表达在肥胖患者的皮下和内脏脂肪组织中较高。肥胖患者的炎症标志物IL-6和C-反应蛋白的血清浓度高于瘦对照组。通过稳态模型评估胰岛素抵抗指数,肥胖患者显示胰岛素抵抗增加,血浆脂联素浓度降低。肥胖组脂肪组织中许多CC趋化因子及其受体的表达与CD68表达呈正相关。结论:肥胖患者脂肪组织中CC趋化因子及其受体表达上调,并与全身炎症反应增加有关。
Background/Aims: Obesity is associated with a low-grade inflammation, insulin resistance, and macrophage infiltration of adipose tissue. The role of CC chemokines and their respective receptors in human adipose tissue inflammation remains to be determined.Methods: sc and visceral adipose tissue of obese patients (body mass index 53.1 +/- 11.3 kg/m(2)) compared with lean controls (body mass index 25.9 +/- 3.8 kg/m2) was analyzed for alterations in inflammatory gene expression.Results: Macrophage infiltration was increased in sc and visceral adipose tissue of obese patients as determined by increased mRNA expression of a macrophage-specific marker (CD68) and by elevated macrophage infiltration. Gene expression of CC chemokines involved in monocyte chemotaxis (CCL2, CCL3, CCL5, CCL7, CCL8, and CCL11) and their receptors (CCR1, CCR2, CCR3, and CCR5) was higher in sc and visceral adipose tissue of obese patients. Serum concentrations of the inflammatory marker IL-6 and C-reactive protein were elevated in obese patients compared with lean controls. Obese patients revealed increased insulin resistance as assessed by the homeostasis model assessment of insulin resistance index and reduced plasma adiponectin concentrations. Adipose tissue expression of many CC chemokines and their receptors in the obese group positively correlated with CD68 expression.Conclusion: Up-regulation of the CC chemokines and their respective receptors in adipose tissue occurs in human obesity and is associated with increased systemic inflammation.