肥胖会导致脂肪组织的炎症免疫反应，从而加强胰岛素耐受、促进II型糖尿病的发生；然而免疫细胞调节代谢平衡及肥胖发生的相关机制至今尚不完全清楚。我们已有的研究发现，在调节性T细胞（Treg）中特异性地敲除转录抑制因子NCoR1将显著地阻止年龄依赖的或者高脂饮食诱导的肥胖发生，并影响外周免疫器官中Treg细胞比例、Nrp1和IL-33受体ST2的表达水平，说明NCoR1可能通过调控Treg的数量和功能，从而调控代谢平衡和肥胖的发生。本项目拟在此研究基础上，深入研究NCoR1对外周Treg的分化、功能和维持的调控机制，阐明NCoR1缺失的Treg对代谢平衡的调控作用以及抑制肥胖发生的机理，为肥胖的免疫调控机制提供新的理论认识，为预防和治疗肥胖及II型糖尿病等相关疾病提供理论支撑。

Obesity is steadily increasing in China with rapid improvement of people’s living quality. Obesity is tightly associated with cardiovascular disease, type II diabetes, osteoarthritis, and several forms of cancer. These comorbidities together with obesity per se have increasingly become a major health issue in recent decades. It is known that low-grade inflammation in adipose tissues caused by obesity is a critical risk factor that contributes to these comorbidities. However, how immune cells balance host metabolism and affect the development of obesity still remains largely unknown. Our preliminary studies revealed that mice deficient for transcriptional repressor NCoR1 specifically in regulatory T cells (Tregs) were resistant to both age-dependent and high-fat diet-induced obesity. NCoR1 deletion specifically affects the peripheral rate of Tregs and their expression of Nrp1 and ST2, the receptor of IL-33, which may mediate the metabolism balance regulated by Treg. This project is aimed at further studying how NCoR1 regulates the function and maintenance of Tregs and how NCoR1-deficient Tregs modulate the metabolism balance and restrict the development of obesity. We hope our study will ultimately lead to a better understanding of the relationship between immune cells and metabolism disorder and provide a novel basis for the prevention and treatment of obesity, type II diabetes and other related diseases.