IL-27 signalling promotes adipocyte thermogenesis and energy expenditure.

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.

• Authors: 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, Zhinan Yin
• Journal: Nature (Nature) Vol. 600 Issue 7888 Pg. 314-318 (12 2021) ISSN: 1476-4687 [Electronic] England
• PMID: 34819664 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Il27ra protein, mouse
• Interleukin-27
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, mouse
• Receptors, Interleukin
• Ucp1 protein, mouse
• Uncoupling Protein 1
• p38 Mitogen-Activated Protein Kinases

Topics

• Adipocytes (metabolism)
• Animals
• Bariatric Surgery
• Disease Models, Animal
• Energy Metabolism
• Female
• Humans
• Insulin Resistance
• Interleukin-27 (blood, metabolism, therapeutic use)
• Male
• Mice
• Obesity (blood, drug therapy, metabolism, prevention & control)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (metabolism)
• Receptors, Interleukin (metabolism)
• Signal Transduction
• Thermogenesis
• Uncoupling Protein 1 (biosynthesis)
• p38 Mitogen-Activated Protein Kinases (metabolism)