LXRα信号通路介导低盐胁迫致大菱鲆肝脏脂代谢紊乱的作用机制研究

盐度改变是水产养殖中重要的环境胁迫因素，可增加机体渗透调节压力，诱发机体能量代谢异常，但基于能量利用和供给角度探索水生动物应对盐度胁迫的适应性机制仍十分缺乏和薄弱。项目组前期研究发现，急性低盐胁迫会导致大菱鲆肝脏脂代谢紊乱，且伴随肝X受体α(LXRα)信号通路异常活跃，推测LXRα信号通路介导了此紊乱过程。基于此，本项目以大菱鲆为研究对象，聚焦LXRα信号通路，采用现代生物技术，从体内和体外两个方向对LXRα进行激活和干扰，以明确其在低盐胁迫下对脂质代谢的调控作用。同时结合多组学分析，解析低盐胁迫下LXRα信号通路调控脂代谢的分子网络路径，从个体、组织到分子水平深入探索低盐胁迫、脂代谢及LXRα信号通路三者的相互关系。研究成果将阐明LXRα信号通路介导低盐胁迫致大菱鲆肝脂代谢紊乱的作用机制，从新的角度诠释鱼类盐度适应机制，丰富鱼类胁迫生理学内容，并为大菱鲆耐低盐良种选育提供理论和技术支撑。

Salinity change is an important environmental stress factor in the process of aquaculture. It can increase difficulty in osmoregulation and induce abnormal energy metabolism. However, the study on the adaptive mechanism of aquatic animals under salinity stress from the perspective of energy utilization and supply is still very scarce and weak. Our previous research found that acute low salt stress can lead to lipid metabolism disorder in the liver of turbot, accompanied by the abnormal activity of LXRα signal pathway. It is speculated that LXRα signaling pathway mediates the metabolism disorder process. In this project, following the guiding hypothesis the salinity stress leads to cellular energy metabolism change, the LXRα signal pathway obtained in the early stage which is closely related to lipid metabolism will be systematically studied. Focusing on LXRα signal pathway, modern biotechnology was used to clarify its regulatory effect on lipid metabolism by activating and inhibiting LXRα from both in vivo and in vitro. Meanwhile, the molecular network pathway of LXRα signaling pathway regulating lipid metabolism under low salt stress will be further explored through combining with the transcriptomics and metabolomics analysis. The relationship among low salt stress, lipid metabolism and LXRα signal pathway will be explored from individual, tissue and molecular level. Results and conclusion of this study will systematically elucidate the mechanism of liver lipid metabolism disorder of turbot under low salt stress through LXR α signal pathway. It can also explain the mechanism of salinity adaptation of aquatic animals from a new perspective and enrich the physiological content of fish stress. Moreover, results can provide theoretical and technical support for the breeding of turbot with low salt tolerance.