IL-27 signalling promotes adipocyte thermogenesis and energy expenditure

Qian Wang, Dehai Li, Guangchao Cao, Qiping Shi, Jing Zhu, Mingyue Zhang, Hao Cheng, Qiong Wen, Hao Xu, Leqing Zhu, Hua Zhang, Rachel J. Perry, Olga Spadaro, Yunfan Yang, Shengqi He, Yong Chen, Baocheng Wang, Guangqiang Li, Zonghua Liu, Caixian Yang, Xiaoli Wu, Libing Zhou, Qinghua Zhou, Zhenyu Ju, Hongyun Lu, Yongjie Xin, Xiaoyong Yang, Cunchuan Wang, Yong Liu, Gerald I. Shulman, Vishwa Deep Dixit, Ligong Lu (), Hengwen Yang (), Richard A. Flavell () and Zhinan Yin ()
Additional contact information
Qian Wang: Jinan University
Dehai Li: Jinan University
Guangchao Cao: Jinan University
Qiping Shi: Jinan University
Jing Zhu: Jinan University
Mingyue Zhang: Jinan University
Hao Cheng: Shanghai Jiao Tong University
Qiong Wen: Jinan University
Hao Xu: School of Medicine, Yale University
Leqing Zhu: Jinan University
Hua Zhang: Jinan University
Rachel J. Perry: Yale University
Olga Spadaro: School of Medicine, Yale University
Yunfan Yang: School of Medicine, Yale University
Shengqi He: Wuhan University
Yong Chen: Wuhan University
Baocheng Wang: Tsinghua University
Guangqiang Li: Jinan University
Zonghua Liu: Jinan University
Caixian Yang: Department of Endocrine, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People’s Hospital
Xiaoli Wu: Tianjin University
Libing Zhou: Jinan University
Qinghua Zhou: Jinan University
Zhenyu Ju: Jinan University
Hongyun Lu: Jinan University
Yongjie Xin: Jinan University
Xiaoyong Yang: School of Medicine, Yale University
Cunchuan Wang: The First Affiliated Hospital of Jinan University
Yong Liu: Wuhan University
Gerald I. Shulman: Yale University
Vishwa Deep Dixit: School of Medicine, Yale University
Ligong Lu: Jinan University
Hengwen Yang: Jinan University
Richard A. Flavell: School of Medicine, Yale University
Zhinan Yin: Jinan University

Nature, 2021, vol. 600, issue 7888, 314-318

Abstract: Abstract Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes1,2. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized3–6. Here we define a critical role of IL-27–IL-27Rα signalling in improving thermogenesis, protecting against diet-induced obesity and ameliorating insulin resistance. Mechanistic studies demonstrate that IL-27 directly targets adipocytes, activating p38 MAPK–PGC-1α signalling and stimulating the production of UCP1. Notably, therapeutic administration of IL-27 ameliorated metabolic morbidities in well-established mouse models of obesity. Consistently, individuals with obesity show significantly decreased levels of serum IL-27, which can be restored after bariatric surgery. Collectively, these findings show that IL-27 has an important role in orchestrating metabolic programs, and is a highly promising target for anti-obesity immunotherapy.

Date: 2021
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DOI: 10.1038/s41586-021-04127-5

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