低温环境暴露下机体自主产热不足、核心体温降低，导致低体温发生，严重影响寒区人员作业能力与生命健康。解耦连蛋白UCP1是机体关键产热分子，是预防低体温发生的关键蛋白。申请人前期工作检测低温暴露过程中UCP1分子的表达变化特征，发现在急性低温暴露中UCP1表达水平受RNA结合蛋白转录后调控。通过对靶分子UCP1的生物信息学分析，并结合低温暴露棕色脂肪表达谱差异基因分析，筛选获得低温暴露表达显著增高的RNA结合蛋白HuR。本项目以HuR分子为切入点，揭示低温暴露下HuR负向调节UCP1表达的分子机制，明确靶向干预HuR分子促进棕色脂肪产热代谢抵抗低体温发生的功能作用，进一步证明HuR小分子抑制剂MS-444在提升机体御寒能力中的重要作用。该研究项目，从理论上阐明低温暴露机体产热代谢的分子调控新机制，从实际应用上为低温环境低体温防护研究提供有效靶点与干预药物，为保障寒区人员作业安全奠定基础。

In cold environment, the insufficient heat production and the lower core body temperature will result in hypothermia, which seriously affects the working ability and life health. Uncoupling protein UCP1 is a key thermogenic molecule for increasing heat production and preventing hypothermia. Our previous work examined the change pattern of UCP1 during cold exposure, and found that the protein level of UCP1 is predominantly controlled by post-transcriptional regulatory RNA binding protein, especially upon acute cold exposure. Combined with cold-induced changed genes analysis and UCP1 potential targets bioinformatics analysis, we screened out the RNA-binding protein HuR. The aim of this study is to reveal the post-transcriptional regulatory mechanism of HuR in inhibiting UCP1 expression under acute cold exposure, to clarify the function that blocking HuR promotes brown fat thermogenesis to defend hypothermia, and to prove that the agent MS-444, as a HuR inhibitor, plays an important role in improving cold adaptation and preventing hypothermia. This project theoretically elucidates a new molecular regulatory mechanism of body thermogenic metabolism under cold environment, and provides a potential target and intervention drug for the protection of cold-induced hypothermia.