基础代谢异常是导致肥胖症的独立危险因素，目前对其分子调控机制研究较少。前期发现Riz1基因敲除小鼠肥胖并且基础代谢降低；使用RNA-Seq方法筛选到RIZ1调控靶基因Ubiad1，初步证明RIZ1通过结合UBIAD1启动子区域调控该基因表达。同时，RIZ1也可通过结合AKT3启动子区域调控AKT3表达进而抑制AKT/mTOR及其下游信号通路。文献报道UBIAD1和AKT3参与调控基础代谢和能量合成。据此本研究提出RIZ1通过UBIAD1和AKT3共调控肥胖基础代谢的科学假说。本课题拟采用基因干扰或过表达、EMSA、RNA-Seq等方法在细胞和动物模型中试图阐明RIZ1通过UBIAD1和AKT3共调控网络调节肥胖基础代谢的分子机制。本项目的实施将提供一条新的基础代谢影响肥胖的分子通路，同时也为未来基于RIZ1为靶点开发治疗肥胖症药物提供实验依据。

Basal metabolic abnormalities were independent risk factors leading to obesity, and little research had been done on their molecular regulatory mechanisms. Our previous study found the Riz1 knockout mice obesity and the basal metabolism decreased; The Ubiad1 gene regulated by RIZ1 was identified using RNA-Seq method, and RIZ1 regulated the gene expression of Ubiad1 by binding to the promoter region. At the same time, RIZ1 can also regulate AKT3 expression by binding the AKT3 promoter region to further inhibit AKT/mTOR and its downstream signaling pathways. The literature reported that UBIAD1 and AKT3 were involved in regulating basal metabolism and energy synthesis. Based on this, we proposed a scientific hypothesis that RIZ1 regulated basal metabolism of obesity through UBIAD1 and AKT3. In this study, we attempt to elucidate the molecular mechanism of RIZ1 regulating cellular basic metabolism through UBIAD1 and AKT3 co-regulatory networks by using gene interference or overexpression, EMSA and RNA-Seq methods in cell and animal models. The implementation of this project will provide a new molecular pathway for basal metabolism to affect obesity, and also provide experimental evidence for the development of anti-obesity drugs based on RIZ1 in the future.