Blocking IL-6 trans-Signaling Prevents High-Fat Diet-Induced Adipose Tissue Macrophage Recruitment but Does Not Improve Insulin Resistance
- Author(s)
- Kraakman, MJ; Kammoun, HL; Allen, TL; Deswaerte, V; Henstridge, DC; Estevez, E; Matthews, VB; Neill, B; White, DA; Murphy, AJ; Peijs, L; Yang, C; Risis, S; Bruce, CR; Du, XJ; Bobik, A; Lee-Young, RS; Kingwell, BA; Vasanthakumar, A; Shi, W; Kallies, A; Lancaster, GI; Rose-John, S; Febbraio, MA;
- Details
- Publication Year 2015-03-03,Volume 21,Issue #3,Page 403-416
- Journal Title
- Cell Metab
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- Cell Press
- Research Division(s)
- Molecular Immunology
- PubMed ID
- 25738456
- Publisher's Version
- https://doi.org/10.1016/j.cmet.2015.02.006
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-03-06 11:41:46
Last Modified: 2016-04-20 11:39:55