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中文摘要：
糖脂代谢紊乱与心血管疾病、糖尿病、肥胖、脂肪肝等疾病的发生密切相关。糖脂代谢调控是多方面、多层次的，包括胆固醇合成代谢调控、内质网应激（ER-Stress） 调控、线粒体功能异常调控等。许多小分子化合物能够作用于以上不同调控通路中的关键节点，调控糖脂代谢。本集成项目以前期已经筛选出的具有调控活性的小分子化合物为基础，设计合成探针，阐明胆固醇合成途径、内质网应激中的IRE1α-XBP1和FXR信号通路、线粒体功能异常蛋白UCP2调控通路、酸化引发的信号转导途径中的重要蛋白因子和关键靶点，探索新的糖脂代谢平衡调控机制。并对高活性的小分子化合物进行结构优化，解析其结构，旨在开发出先导化合物。在动物水平上，利用动脉粥样硬化、糖尿病、肥胖等疾病小鼠模型上评价其逆转糖脂代谢紊乱的功能，为进一步开发治疗糖脂代谢紊乱的药物奠定基础。
结论摘要：
英文主题词Glucose and Lipid Metabolism；Small Molecular Probes；ER stress；Cholesterol；
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