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Expression of activating transcription factor 2 in inflammatory macrophages in obese adipose tissue
Author(s) -
Miyata Yugo,
Fukuhara Atsunori,
Otsuki Michio,
Shimomura Iichiro
Publication year - 2013
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20274
Subject(s) - activating transcription factor , transcription factor , inflammation , lipopolysaccharide , adipose tissue macrophages , proinflammatory cytokine , activating transcription factor 2 , adipose tissue , white adipose tissue , tumor necrosis factor alpha , microbiology and biotechnology , phosphorylation , cd11c , u937 cell , chemistry , endocrinology , medicine , biology , immunology , gene expression , promoter , apoptosis , phenotype , biochemistry , gene
Objective: 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 H 2 O 2 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. Conclusions: These results suggest that ATF2 is an important transcriptional factor relating to inflammation through the suppression of ATF3 in M1 macrophages of WAT.