下丘脑弓状核摄食神经元与肝郁脾虚证食欲减退密切相关，但何种机制调控摄食神经元引起食欲减退，仍不清楚。申请人前期用全基因组DNA甲基化和转录组测序，在肝郁脾虚证摄食中枢—下丘脑弓状核筛选到重要分子Fam111a，其抑制食欲可能与促进下丘脑神经再生，继而激活LepRb-STAT3信号通路，从而上调抑食欲神经元POMC有关。因此，我们提出假说：肝郁脾虚证食欲减退的生物学基础与下丘脑弓状核Fam111a介导LepRb-STAT3信号通路调控摄食神经元有关。本项目拟通过体内复制肝郁脾虚证模型、体外建立下丘脑神经再生模型、逍遥散以方测证，运用过表达和沉默下丘脑Fam111a、免疫荧光双标、免疫印迹、RT-qPCR等方法，从动物和细胞两个水平、正反两个方面探究Fam111a介导LepRb-STAT3信号通路调控摄食神经元与肝郁脾虚证食欲减退相关。这对于揭示肝郁脾虚证食欲减退科学内涵有重要意义。

The feeding neurons in hypothalamic arcuate nucleus is closely related to the appetite loss of liver stagnation and spleen deficiency syndrome, but it is still unclear which mechanism regulates the feeding neurons and causes appetite loss in liver stagnation and spleen deficiency syndrome. We used the whole genome DNA methylation and transcriptome sequencing to screen the target molecule Fam111a in the feeding center-hypothalamic arcuate nucleus, which regulates appetite and promotes hypothalamic neurogenesis, and increases hypothalamic neurons to LepRb-STAT3. The sensitivity of the signaling pathway is thus associated with up-regulation of the anorexia neuron POMC. Therefore, we propose a hypothesis: the biological basis of appetite loss in liver stagnation and spleen deficiency syndrome is related to the regulation of the feeding neurons by the Fam111a-mediated LepRb-STAT3 signaling pathway in the hypothalamic arcuate nucleus. This project intends to replicate the rat model of liver stagnation and spleen deficiency in vivo, establish a hypothalamic neurogenesis cell model in vitro, and use Xiaoyao San to test the syndrome model, use overexpression and silence hypothalamic Fam111a, immunofluorescence double label, western blot and RT-qPCR, to research the biological basis of appetite loss in liver stagnation and spleen deficiency syndrome from Fam111a-mediated LepRb-STAT3 signaling pathway in the regulation of feeding neurons. This is of great significance for revealing the scientific connotation of appetite loss in liver stagnation and spleen deficiency syndrome.