假结核耶尔森氏菌VI型分泌系统效应蛋白TseL调节小鼠肥胖的机制研究

肥胖已经成为一个日益严峻的全球性公共卫生问题，肠道微生物在肥胖发生中扮演重要角色，但目前关于肠道微生物通过何种方式影响肥胖及其分子机制所知甚少。本项目将在肠道细菌假结核耶尔森氏菌VI型分泌系统效应蛋白TseL影响小鼠肥胖这一重要发现基础上，综合利用转录组学、代谢组学和靶标蛋白筛选等技术，筛选TseL在宿主体内作用的靶标蛋白，揭示受其影响的肥胖相关信号通路和代谢途径，比较其与瘦素作用机制的异同。本项目将从分子水平揭示细菌效应蛋白TseL调节小鼠肥胖的机制，以深化当前对肠道细菌与宿主肥胖关系的认识，为治疗肥胖症和相关病症提供新的靶点，并为研究肠道菌群与宿主的相互作用提供新的思路。此外，本项目对认识VI型分泌系统效应蛋白的新功能也具有重要意义。

Obesity has become a serious global public health issue and gut microbiota plays a critical role in the development of obesity. However, how gut microbiota affects obesity and the underlying molecular mechanisms remain to be clarified. Our previous work showed that TseL, an effector from the intestinal bacteria Yersinia pseudotuberculosis type VI secretion system (T6SS) has the ability to regulate obesity in mice. Based on this novel finding, in this study we planned to combine the transcriptome, metabolome and target protein screening approaches to identify the host target protein of TseL and reveal the possible obesity-related signaling pathways and metabolic pathways affected by TseL and compare its mechanisms of action with leptin. This study will elucidate the mechanism of effector TseL in regulating obesity in mice at the molecular level and deepen the current understanding about the relationship between gut microbiota and obesity. This could provide new therapeutic targets for the treatment of obesity and related diseases and new concepts for the study of gut microbiota-host interactions. In addition, this study also has great importance for understanding of the new functions of T6SS effector.