肥胖状态下，高水平游离脂肪酸(FFA)可激活脂肪细胞NF-кB炎症信号通路。KLF4可促进脂肪酸β氧化，同时与NF-кB活性单位P65结合抑制炎症，KLF4表达与TLR9正相关。高水平FFA可使脂肪细胞内DNA甲基转移酶(DNMT)表达量及活性增加。预实验结果表明：肥胖大鼠腹部脂肪组织TLR9/KLF4表达均降低，与FFA及炎症因子水平负相关。推测肥胖状态下，高水平FFA通过增加DNMT表达量及活性抑制TLR9/KLF4表达，促进脂肪细胞炎症反应。本研究在体外培养脂肪细胞及高脂诱导TLR9基因敲除大鼠肥胖模型基础上，观察高浓度FFA对DNMT1/3表达及其活性的影响，以及对TLR9、KLF4基因启动子区DNA甲基化状态及其表达的影响；观察对脂肪细胞脂肪酸氧化能力及炎症反应的影响。探讨TLR9/KLF4抑制脂肪细胞炎症反应的作用机制。为阐明肥胖始动炎症的分子机制提供新的基础理论和实验依据。

Under Obese state, high levels of free fatty acid (FFA) can activate NF-кB inflammatory signaling pathways in adipocytes. KLF4 can promote fatty acid β-oxidation, and it binds with p65, the active unit of NF-кB to inhibit inflammation. KLF4 expression was positively correlated with TLR9. High levels of FFA can make fat cells DNA methyltransferase (DNMT) expression and activity increase. The preliminary data shows that: In abdominal adipose tissue of obese rats, the TLR9 / KLF4 expression level was lower, with the FFA and inflammatory factors levels negatively correlated. Therefore, it was speculated that under obese state, high level of FFA inhibited TLR9 / KLF4 expression by increasing DNMT expression and activity, thus promote fat cell inflammation. In this study, based on in vitro cultured fat cells and fat induced TLR9 knockout rat model of obesity, we observed how high concentrations of FFA effect on DNMT1 / 3 expression and activity, as well as its effect on TLR9, KLF4 gene promoter DNA methylation and expression; in addition, observe the effects of high concentrations of FFA on fatty acid oxidation and inflammatory response of adipocytes. Discover mechanisms of how TLR9 / KLF4 inhibit fat cell inflammatory response, which will provide new theoretical and experimental basis to clarify the molecular mechanisms of how obesity initiates inflammation.