title: Expression of activating transcription factor 2 in inflammatory macrophages in obese adipose tissue.
abstract: 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 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.
  
  
  CONCLUSIONS
  These results suggest that ATF2 is an important transcriptional factor relating to inflammation through the suppression of ATF3 in M1 macrophages of WAT.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Yugo
authors.initials: Y
authors.lastname: Miyata
authors.forename: Atsunori
authors.initials: A
authors.lastname: Fukuhara
authors.forename: Michio
authors.initials: M
authors.lastname: Otsuki
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism*; D051700:Activating Transcription Factor 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052436:Adipose Tissue, White / Q000503:physiopathology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D007249:Inflammation / Q000503:physiopathology; D007333:Insulin Resistance; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000503:physiopathology; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000503:physiopathology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D051698:Activating Transcription Factor 2; D051700:Activating Transcription Factor 3; D000893:Anti-Inflammatory Agents; C497106:Atf2 protein, mouse; C103002:Atf3 protein, mouse; D016207:Cytokines; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species