IL-27 signalling promotes adipocyte thermogenesis and energy expenditure
IL-27 signalling promotes adipocyte thermogenesis and energy expenditure
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IL-27 信号传导促进脂肪细胞产热和能量消耗
DOI：
10.1038/s41586-021-04127-5
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发表时间：
2021
期刊：
影响因子：
64.8
通讯作者：
Zhinan Yin
中科院分区：
文献类型：
--
作者：
Qian Wang;Dehai Li;Guangchao Cao;Qiping Shi;Ligong Lu;Hengwen Yang;Richard A. Flavell;Zhinan Yin
棕色和米色脂肪组织中的产热在维持体温和对抗代谢紊乱如肥胖和2型糖尿病的发展方面具有重要作用。尽管人们对棕色和米色脂肪组织的定型和活化有很多了解，但其多种丰富的免疫因子还没有得到很好的表征。在这里，我们定义了IL-27-IL-27 R α信号传导在改善产热、防止饮食诱导的肥胖和改善胰岛素抵抗中的关键作用。机制研究表明，IL-27直接靶向脂肪细胞，激活p38 MAPK-PGC-1α信号传导并刺激UCP 1的产生。值得注意的是，IL-27的治疗性施用改善了良好建立的肥胖症小鼠模型中的代谢发病率。一致地，肥胖个体显示血清IL-27水平显著降低，其可以在减肥手术后恢复。总的来说，这些发现表明IL-27在协调代谢程序中具有重要作用，并且是抗肥胖免疫疗法的非常有前途的靶点。
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.