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Blocking IL-6 trans-signaling prevents high-fat diet-induced adipose tissue macrophage recruitment but does not improve insulin resistance


Kraakman, MJ and Kammoun, HL and Allen, TL and Deswaerte, V and Henstridge, DC and Estevez, E and Matthews, VB and Neill, B and White, DA and Murphy, AJ and Peijs, L and Yang, C and Risis, S and Bruce, CR and Du, X-J and Bobik, A and Lee-Young, RS and Kingwell, BA and Vasanthakumar, A and Shi, W and Kallies, A and Lancaster, GI and Rose-John, S and Febbraio, MA, Blocking IL-6 trans-signaling prevents high-fat diet-induced adipose tissue macrophage recruitment but does not improve insulin resistance, Cell Metabolism, 21, (3) pp. 403-416. ISSN 1550-4131 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 Elsevier Inc.

DOI: doi:10.1016/j.cmet.2015.02.006


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 trans-signaling, 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.

Item Details

Item Type:Refereed Article
Keywords:antiinflammatory agent, CCAAT enhancer binding protein beta, fatty acid binding protein 4, glycoprotein, glycoprotein gp 130, hemoglobin A1c, hypoxia inducible factor 1alpha, I kappa B kinase beta, interleukin 10, interleukin 1beta, interleukin 6
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell metabolism
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Henstridge, DC (Dr Darren Henstridge)
ID Code:133356
Year Published:2015
Web of Science® Times Cited:163
Deposited By:Health Sciences
Deposited On:2019-06-24
Last Modified:2019-07-22

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