作者
Michael J Kraakman, Helene L Kammoun, Tamara L Allen, Virginie Deswaerte, Darren C Henstridge, Emma Estevez, Vance B Matthews, Bronwyn Neill, David A White, Andrew J Murphy, Lone Peijs, Christine Yang, Steve Risis, Clinton R Bruce, Xiao-Jun Du, Alex Bobik, Robert S Lee-Young, Bronwyn A Kingwell, Ajithkumar Vasanthakumar, Wei Shi, Axel Kallies, Graeme I Lancaster, Stefan Rose-John, Mark A Febbraio
发表日期
2015/3/3
期刊
Cell metabolism
卷号
21
期号
3
页码范围
403-416
出版商
Elsevier
简介
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 …
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MJ Kraakman, HL Kammoun, TL Allen, V Deswaerte… - Cell metabolism, 2015