模式识别受体CD36在脂肪组织代谢性炎症发生中的作用及分子机制

项目名称： 模式识别受体CD36在脂肪组织代谢性炎症发生中的作用及分子机制

项目编号： No.81200567

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 赵蕾

作者单位： 重庆医科大学

项目金额： 23万元

中文摘要： 代谢性炎症主要指营养物和代谢过剩所触发的慢性低峰度炎症，与代谢性疾病的发生发展密切相关。代谢性炎症产生的主要器官是脂肪组织，模式识别受体白细胞分化抗原36（CD36）是介导代谢性炎症的重要蛋白。课题组前期发现：高脂状态下，脂肪组织CD36表达上调且伴炎症因子增加；而CD36基因敲除显著降低炎症水平。然而，目前尚不清楚CD36激活脂肪组织代谢性炎症的具体分子机制。有研究报道在小胶质细胞中，CD36能与Lyn激酶和Toll样受体(TLRs)结合而活化NF-κB炎症信号通路，启动无菌性炎症反应。在脂肪组织中，CD36能否也通过与Lyn和TLRs结合而启动代谢性炎症的发生，至今未见报道，值得深入探讨。 本项目拟使用已有的野生型和CD36基因敲除小鼠、脂肪/巨噬细胞体内外模型，深入探讨脂肪组织内CD36/Lyn/TLRs激活代谢性炎症反应的信号转导机制，从一个新的角度阐释代谢性炎症发生的分子机制。

中文关键词： 白细胞分化抗原36；脂肪；代谢性炎症；Toll样受体；胰岛素抵抗

英文摘要： Both adipocytes and macrophages in adipose tissues were involved in the development of metabolic inflammation. Metabolic inflammation in adipose tissues is implicated in development of metabolic diseases, such as type 2 diabetes and atherosclerotic cardiovascular disease. Previous studies indicated that pattern recognition receptor CD36 might be the crosslink of lipid metabolism and inflammation. Our previous studies also has shown that high-fat diet upregulated serum free fatty acids (FFAs) levels (a CD36 ligand) and CD36 expression in adipose tissues of C57BL/6J mice, accompanied with increase levels of inflammatory cytokines in adipose tissues and blood. CD36 gene knock-out significantly ameliorated the high-fat diet induced metabolic inflammation in mice. However the molecular mechanisms by which CD36 activate metabolic inflammation remain unclear. It has been demonstrated that amyloid-β (a CD36 ligand) stimulates sterile inflammation in microglia by activation of CD36-TLR4-TLR6/Lyn pathway. We hypothesize that under metabolic disorders, the increased oxidized LDL and FFAs stimulate CD36 protein expression in adipose tissues which activates NF-κB mediated inflammatory response by recuiting kinase Lyn to the TLR4-TLR6 complex. In this project, the CD36 gene knockout / wild-type mice, adipocytes / macrophages

英文关键词： CD36；adipose tissue；meta-inflammation；Toll-like receptors；insulin resistance