固有免疫在糖脂代谢调节中具有重要作用。炎症不仅参与了β细胞的损伤，也与胰岛素抵抗及2型糖尿病的发生有密切关系；以肥胖为中心的脂代谢紊乱疾病对代谢性炎症的发生有重要影响。然而，代谢性炎症发生的机制及其在糖代谢稳态失衡中的作用还远未阐明。.本课题将重点探讨：1) 肥胖导致脂肪组织产生代谢性炎症的机制；2) 高脂(肪酸)血症是否通过CD36的表达和转录后修饰，调节TLR /NF-κB 信号通路，诱导代谢性炎症产生；3) 脂肪细胞与免疫细胞、肝脏细胞及肌肉细胞等其他组织之间是否通过器官间分子对话，放大和泛化代谢性炎症；4) 代谢性炎症是否通过影响mTOR /S6K 和AMPK 途径，影响胰岛素信号通路，造成β细胞损害，最后导致糖稳态异常。上述研究将为代谢性炎症产生的机制提供新的依据，也将为干预代谢性炎症诱发的糖稳态失衡提供新的思路。

The proportion of obese population is increasing and becoming a huge health problem in China due to the changes of lifestyle and dietary. Gucose homeostasis in obese patients is disrupted by unknown mechanisms. It is well-known that adipose tissue in obese patients secretes large amounts of adipokines, inflammatory cytokines, and miRNAs. Based on our previous studies, this project intend to investigate if 1) adipocytes in obese conditions grows abnormally, causing meta-flammation; 2) hyperlipidaemia (especially high levels of free fatty acids) causes meta-flammation by acting CD36/TLR/NKkB pathway; 3) cross-talks between adipocytes and macrophages and other cells amplify the meta-flammation; 4) meta-flammation disrupts glucose homeostasis by activation of mTOR/S6K and AMPK pathways. The above study provides a new basis for understanding the crosstalk between metabolic inflammation and glucose homeostasis.