Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai, China.
The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, China.
Nature. 2021 Dec;600(7888):314-318. doi: 10.1038/s41586-021-04127-5. Epub 2021 Nov 24.
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 diabetes. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized. 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.
棕色和米色脂肪组织的产热对于维持体温以及对抗肥胖和 2 型糖尿病等代谢紊乱的发生具有重要作用。尽管人们对棕色和米色脂肪组织的分化和激活了解很多，但它的多种丰富的免疫因子尚未得到很好的描述。在这里，我们定义了 IL-27-IL-27Rα 信号在改善产热、预防饮食诱导肥胖和改善胰岛素抵抗方面的关键作用。机制研究表明，IL-27 直接靶向脂肪细胞，激活 p38 MAPK-PGC-1α 信号通路，并刺激 UCP1 的产生。值得注意的是，IL-27 的治疗性给药改善了肥胖的既定小鼠模型中的代谢紊乱。同样，肥胖个体的血清 IL-27 水平显著降低，而减肥手术后可以恢复。总之，这些发现表明 IL-27 在协调代谢程序方面具有重要作用，是肥胖症免疫治疗的一个很有前途的靶点。
