Irisin介导减重改善颏舌肌线粒体功能的作用及分子机制

Obesity is an important risk factor for the occurrence of OSAHS. In our previous study, the improved ratio for OSAHS after the weight reduction by bariatric surgery was up to 80%.The current theory indicates that weight reduction might alleviate OSAHS through the improvement of the structure and function of the upper airway muscles. However, there is little evidence to explain the potential mechanism. Irisin is a newly reported endocrine factor, which could increase the mitochondrial content, the strength of skeletal muscle and the energy metabolism. Therefore, it has caused widespread concern. Our previous study found the change of Irisin correlated significantly with the change of body mass index and the severity of OSAHS after the bariatric surgery. In the pilot study, we found Irisin could increase the copy number of mtDNA and the oxidative metabolism of C2C12 myocytes. These evidence might indicate the interaction among weight reduction, Irisin and the mitochondrial function of skeletal muscle. Therefore, we designed a study to explore the effect and molecular mechanisms of Irisin acts on the function of genioglossus mitochondrion, which might provide evidence for the pathogenesis and potential therapeutic targets for OSAHS.

肥胖是阻塞性睡眠呼吸暂停低通气综合征（OSAHS）主要风险因素之一。项目组前期研究证实减重手术对肥胖人群的OSAHS改善率高达80%。目前的理论认为，减重可能通过改变上气道肌群的结构和功能，达到改善OSAHS的作用。但是，尚无充分的证据揭示其作用机制。鸢尾素(Irisin)是一种新发现的内分泌因子，有增加细胞内线粒体含量、增强骨骼肌力量以及能量代谢的作用，受到了多个学科的广泛关注。项目组通过临床检验，发现减重手术后血清Irisin浓度的变化与BMI和OSAHS严重程度的变化显著相关。预实验中，项目组证实Irisin可增加C2C12成肌细胞内线粒体DNA含量及其氧化能力。以上证据提示减重、Irisin以及线粒体功能之间可能存在交互作用。因此，本项目拟在前期研究的基础上，探索Irisin在减重改善颏舌肌线粒体功能中的作用及可能机制，从而为寻找OSAHS的发病机制及潜在治疗靶点提供依据。