title: Histone demethylase KDM1A represses inflammatory gene expression in preadipocytes.
abstract: OBJECTIVE
  Persistent inflammation and impaired adipogenesis are frequent features of obesity and underlie the development of its complications. However, the factors behind adipose tissue dysfunction are not completely understood. Previously it was shown that histone demethylase KDM1A is required for adipogenesis.
  
  
  METHODS
  Kdm1a expression was knocked down in 3T3-L1 preadipocytes by siRNA transfection and whole-genome expression profiling was performed by microarray hybridization. The role of NF-κβ and C/EBPβ was analyzed by incubation with the inhibitor parthenolide and by cebpb knockdown, respectively.
  
  
  RESULTS
  Knockdown of kdm1a or rcor2 in 3T3-L1 preadipocytes results in impaired differentiation and induction of inflammatory gene expression. Enhanced expression of il6 in kdm1a knocked down preadipocytes is associated with increased recruitment of C/EBPβ and the NF-κβ subunit RelA to the il6 promoter. Cebpb knockdown attenuates the induction of il6 expression in kdm1a knocked down cells, whereas simultaneous cebpb knockdown and NF-κβ inhibition abrogates it. Dietary-induced and genetic mouse models of obesity display decreased KDM1A in adipose tissue, and this correlates with increased expression of proinflammatory genes and C/EBPβ.
  
  
  CONCLUSIONS
  KDM1A represses the expression of inflammatory genes in preadipocytes. Dysregulated kdm1a expression in preadipocytes may thus participate in the development of obesity-associated inflammation.
authors.affiliation: Diabetes and Obesity Laboratory, IDIBAPS, CIBERDEM, Barcelona, Spain; Endocrinology and Nutrition Unit, Hospital Clínic, Barcelona, Spain.
authors.forename: Felicia A
authors.initials: FA
authors.lastname: Hanzu
authors.forename: Melina M
authors.initials: MM
authors.lastname: Musri
authors.forename: Alvaro
authors.initials: A
authors.lastname: Sánchez-Herrero
authors.forename: Marc
authors.initials: M
authors.lastname: Claret
authors.forename: Yaiza
authors.initials: Y
authors.lastname: Esteban
authors.forename: Perla
authors.initials: P
authors.lastname: Kaliman
authors.forename: Ramon
authors.initials: R
authors.lastname: Gomis
authors.forename: Marcelina
authors.initials: M
authors.lastname: Párrizas
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D056970:Co-Repressor Proteins; D042783:Endothelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; C545013:Cebpb protein, mouse; D056970:Co-Repressor Proteins; D015850:Interleukin-6; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C485650:Rcor2 protein, mouse; D012097:Repressor Proteins; D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D010089:Oxidoreductases, N-Demethylating