胰岛素抵抗(IR)及高雄激素血症是引发多囊卵巢综合征(PCOS)的核心，代谢手术在减重、改善代谢及生育力障碍中的作用初显，寻找其作用靶点可规避手术风险并扩大临床应用。PCOS时血Nesfatin-1(NES-1)减少，申请者读博士期间发现代谢手术后胃激素NES-1明显升高，上调外周NES-1可改善小鼠PCOS的IR和高雄激素血症。结合NES-1通过激活AMPK参与改善糖脂代谢及激活AMPK下调mTOR可抑制卵泡膜细胞增殖和雄激素分泌，故推测NES-1可能通过激活AMPK改善机体靶器官胰岛素敏感性、抑制卵巢雄激素分泌而改善PCOS。本项目拟对PCOS小鼠外源给予NES-1，借助在体及离体培养手段，明确NES-1改善代谢紊乱所致PCOS的作用，探讨AMPK/mTOR信号通路参与的机制，并采用单细胞测序来初步明确NES-1作用下的膜细胞转录组差异基因表达。希冀为临床防治PCOS提供新的科学依据。

Insulin resistance (IR) and hyperandrogenism are the core of polycystic ovary syndrome (PCOS). The role of metabolic surgery in weight loss, improvement of metabolic and fertility disorders begins to appear, and the research of targets can be avoided the risk of surgery and the expansion of clinical applications. Blood Nesfatin-1 was reduced during PCOS. Applicants learned that Nesfatin-1 was significantly elevated after metabolic surgery and that peripheral Nesfatin-1 improved PCOS’s IR and hyperandrogenism in mice. Nesfatin-1 could active AMPK to improve glucose and lipid metabolism and the activation of AMPK can inhibit the proliferation of theca cells and the secretion of androgen. It is speculated that Nesfatin-1 may improve the insulin sensitivity of the target organs and inhibit the secretion of androgens by the activation of AMPK to improve PCOS. Therefore, it is proposed that exogenous Nesfatin-1 be administered to PCOS mice. With the help of in vivo and in vitro culture methods, it is clear that Nesfatin-1 can improve the function of PCOS caused by metabolic disorders. To explore the mechanism involved in AMPK/mTOR signaling pathway, and single cell sequencing was used to preliminarily identify the transcriptome differential gene expression of membrane cells under the action of Nesfatin-1. We hope to provide a new theoretical basis and scientific basis for clinical prevention and treatment of PCOS.