title: Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ Signaling.
abstract: OBJECTIVE
  Comparative gene identification-58 (CGI-58), an adipose triglyceride lipase (ATGL) coactivator, strongly promotes ATGL-mediated triglyceride (TG) catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CGI-58 in the regulation of inflammatory responsiveness in macrophages.
  
  
  METHODS
  Macrophage-specific GCI-58 transgenic mice (TG) and wild type mice (WT) were fed a high fat diet (HFD), and RAW264.7 cells were treated with lipopolysaccharide (LPS). The peroxisome proliferator-activated receptor (PPAR) signaling was detected. The inflammatory responsiveness and mitochondrial function were examined.
  
  
  RESULTS
  TG mice showed lower serum levels of proinflammatory cytokines and better mitochondrial function in macrophages compared with WT control. Knockdown of CGI-58 in RAW264.7 cells aggravated LPS-induced inflammation and mitochondrial dysfunction. CGI-58 overexpression and silencing in macrophages induced and inhibited PPARγ expression and activity, respectively. Most importantly, the PPARγ-specific agonist rosiglitazone significantly suppressed inflammation and mitochondrial dysfunction induced by CGI-58 deficiency. Furthermore, knockdown of PPARγ in macrophages significantly dampened the role of CGI-58 in suppression of inflammation and mitochondrial dysfunction. Interestingly, CGI-58 inhibited histone deacetylation and the recruitment of histone deacetylase (HDAC) to the PPARγ promoter. Finally, ATGL deficiency did not affect inflammatory responsiveness and PPARγ signaling in macrophages.
  
  
  CONCLUSIONS
  These results demonstrate that macrophage CGI-58 enhances PPARγ signaling and thus suppresses inflammatory responsiveness and mitochondrial dysfunction.
authors.affiliation: Department of Computational Biology and Bioinformatics, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Haimei
authors.initials: H
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Zeng
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.forename: Xincun
authors.initials: X
authors.lastname: Wang
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D007249:Inflammation / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000276:immunology; D047495:PPAR gamma / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000276:immunology; D015398:Signal Transduction
chemical_list: D008070:Lipopolysaccharides; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C492986:Abhd5 protein, mouse