寒冷环境中急性心血管事件发生率显著增加，而脂肪代谢在冷刺激下发生显著变化。我们的前期研究结果发现，冷刺激可以迅速活化BAT，将WAT转变为BRITE，显著加剧AS进程，证实冷刺激通过改变脂肪组织代谢状态而显著影响AS进程。因此进一步研究冷刺激是如何改变脂肪组织代谢状态，是否可通过调控其中某些环节而改善AS病变成为重要的科学问题。本项目结合文献报道和前期研究结果，选取新发现的代谢调节因子FGF21作为研究靶点。使用apoE-/-小鼠和apoE-/-/UCP1-/-小鼠构建的冷刺激模型，研究FGF21对脂肪组织和AS斑块的影响；FGF21是否参与冷刺激诱导的脂肪组织代谢而影响AS进程；FGF21对脂肪组织和AS进程的影响是否依赖于UCP1；及其具体机制。本课题的实施将进一步阐明冷刺激诱导的脂肪代谢改变与AS间的作用以及其发生机制，为AS相关疾病提供新的防治靶点。

Acute cardiovascular events incidence was significantly increased in the cold environment，meanwhile the adipose tissue especially the BAT also experience great metabolic changes under cold stress. Our preliminary results showed that cold stress could quickly acitivate BAT, and convert WAT into BRITE, significantly aggravate development of atherosclerosis, and promote the plaque growth, all these imply that the metabolic change of adipose tissue induced by cold stress may participate in the development of atherosclerosis. Therefore further mechanistic study of how cold-induced metabolic changes of adipose tissue aggravate the development of atherosclerosis is urgently needed, the essential scientific question here is to find a proper target to manipulate this regulatory pathway and ameliorate atherosclerotic leision. According to our former study and some recent researchs, we choose the newly discovered metabolic regulator FGF21 as the study target. The present study uses apoE-/- mice and apoE-/-/UCP1-/-mice with cold stimulation model to study if cold impact the experession level of FGF21, the influence of FGF21 on adipose tissue and atherosclerosis, in attempt to confirm the effects and clarify the possible mechanism of FGF21 induced activation of BAT and the WAT-BRITE conversion on the progress of AS and its plauqe stability. Then we delete the UCP1 gene from the apoE-/- mice to find out exact which kind of role the UCP1 plays in this study. This project will provide further understanding of the effects and molecular mechanism between cold-induced-metabolic changes of adipose tissue and atherosclerosis, offer novel therapeutic targets for atherosclerosis related diseases.