Blocking IL-6 trans-Signaling Prevents High-Fat Diet-Induced Adipose Tissue Macrophage Recruitment but Does Not Improve Insulin Resistance

被引：264

作者：

Kraakman, Michael J. ^{[1
]}

Kammoun, Helene L. ^{[1
]}

Allen, Tamara L. ^{[1
]}

Deswaerte, Virginie ^{[2
]}

Henstridge, Darren C. ^{[1
]}

Estevez, Emma ^{[1
]}

Matthews, Vance B. ^{[1
]}

Neill, Bronwyn ^{[1
]}

White, David A. ^{[3
]}

Murphy, Andrew J. ^{[4
]}

Peijs, Lone ^{[1
]}

Yang, Christine ^{[1
]}

Risis, Steve ^{[1
]}

Bruce, Clinton R. ^{[1
]}

Du, Xiao-Jun ^{[3
]}

Bobik, Alex ^{[2
]}

Lee-Young, Robert S. ^{[1
]}

Kingwell, Bronwyn A. ^{[5
]}

Vasanthakumar, Ajithkumar ^{[6
]}

Shi, Wei ^{[6
,7
]}

Kallies, Axel ^{[6
]}

Lancaster, Graeme I. ^{[1
]}

Rose-John, Stefan ^{[8
]}

Febbraio, Mark A. ^{[1
]}

机构：

[1] BakerIDI Heart & Diabet Inst, Cellular & Mol Metab Lab, Melbourne, Vic 3004, Australia

[2] BakerIDI Heart & Diabet Inst, Vasc Biol & Atherosclerosis Lab, Melbourne, Vic 3004, Australia

[3] BakerIDI Heart & Diabet Inst, Expt Cardiol Lab, Melbourne, Vic 3004, Australia

[4] BakerIDI Heart & Diabet Inst, Haematopoiesis & Leukocyte Biol Lab, Melbourne, Vic 3004, Australia

[5] BakerIDI Heart & Diabet Inst, Metab & Vasc Physiol Lab, Melbourne, Vic 3004, Australia

[6] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia

[7] Univ Melbourne, Dept Comp & Informat Syst, Parkville, Vic 3010, Australia

[8] Univ Kiel, Dept Biochem, D-24098 Kiel, Germany

来源：

CELL METABOLISM | 2015年 / 21卷 / 03期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

MONOCYTE CHEMOATTRACTANT PROTEIN-1; SOLUBLE INTERLEUKIN-6 RECEPTOR; HEPATIC INFLAMMATION; T-CELLS; OBESITY; MICE; ACCUMULATION; INFILTRATION; INHIBITION; BLOCKADE;

D O I：

10.1016/j.cmet.2015.02.006

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Interleukin-6 (IL-6) plays a paradoxical role in inflammation and metabolism. The pro-inflammatory effects of IL-6 are mediated via IL-6 "trans-signaling,'' a process where the soluble form of the IL-6 receptor (sIL-6R) binds IL-6 and activates signaling in inflammatory cells that express the gp130 but not the IL-6 receptor. Here we show that trans-signaling recruits macrophages into adipose tissue (ATM). Moreover, blocking trans-signaling with soluble gp130Fc protein prevents high-fat diet (HFD)-induced ATM accumulation, but does not improve insulin action. Importantly, however, blockade of IL-6 transsignaling, unlike complete ablation of IL-6 signaling, does not exacerbate obesity-induced weight gain, liver steatosis, or insulin resistance. Our data identify the sIL-6R as a critical chemotactic signal for ATM recruitment and suggest that selectively blocking IL-6 trans-signaling may be a more favorable treatment option for inflammatory diseases, compared with current treatments that completely block the action of IL-6 and negatively impact upon metabolic homeostasis.

引用

页码：403 / 416

页数：14

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