Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
Obesity (Silver Spring). 2013 Apr;21(4):731-6. doi: 10.1002/oby.20274.
White adipose tissue (WAT) of obesity is in the state of inflammation with progressive infiltration by macrophages and overproduction of reactive oxygen species (ROS), which can induce WAT dysfunction, including insulin resistance and adipocytokine dysregulation. Activating transcription factor 2 (ATF2) is a member of the ATF/cAMP response element binding family of transcription factors and known to be activated by cellular stressors, such as inflammatory cytokines, lipopolysaccharide (LPS), and ROS. DESIGN AND METHODS, RESULTS: Here, we show that ATF2 protein was significantly more induced in WAT of ob/ob mice compared with C57BL/6J mice. Total and phosphorylated ATF2 were highly expressed in infiltrated macrophages. Furthermore, flow cytometry analysis demonstrated that ATF2 expression was high in CD11c-positive/CD301-negative M1 macrophages. Phosphorylation of ATF2 was induced by treatment with either H2 O2 or LPS in RAW264.7 macrophage cells, and suppression of ATF2 expression by small-interfering RNA induced mRNA levels of ATF3, an anti-inflammatory molecule in macrophages in WAT.
These results suggest that ATF2 is an important transcriptional factor relating to inflammation through the suppression of ATF3 in M1 macrophages of WAT.
肥胖症的白色脂肪组织（WAT）处于炎症状态，巨噬细胞逐渐浸润，活性氧（ROS）过度产生，这会导致 WAT 功能障碍，包括胰岛素抵抗和脂肪细胞因子失调。激活转录因子 2（ATF2）是 ATF/cAMP 反应元件结合家族转录因子的成员，已知其可被细胞应激源（如炎性细胞因子、脂多糖（LPS）和 ROS）激活。
结果显示，ob/ob 小鼠的 WAT 中 ATF2 蛋白的诱导明显高于 C57BL/6J 小鼠。总 ATF2 和磷酸化 ATF2 在浸润的巨噬细胞中高度表达。此外，流式细胞术分析表明，CD11c 阳性/CD301 阴性 M1 巨噬细胞中 ATF2 表达水平较高。H2O2 或 LPS 处理可诱导 RAW264.7 巨噬细胞中 ATF2 的磷酸化，而 WAT 中 M1 巨噬细胞中 ATF2 表达的小干扰 RNA 抑制可诱导抗炎分子 ATF3 的 mRNA 水平升高。
这些结果表明，ATF2 是一种重要的转录因子，通过抑制 WAT 中 M1 巨噬细胞中的 ATF3 与炎症有关。
