title: MAFB as a novel regulator of human adipose tissue inflammation.
abstract: OBJECTIVE
  Dysregulated expression of metabolic and inflammatory genes is a prominent consequence of obesity causing insulin resistance and type 2 diabetes. Finding causative factors is essential to understanding progression of these pathologies and discovering new therapeutic targets. The transcription factor V-maf musculoaponeurotic fibrosarcoma oncogene homologue B (MAFB) is highly expressed in human white adipose tissue (WAT). However, its role in the regulation of WAT function is elusive. We aimed to characterise MAFB expression and function in human WAT in the context of obesity and insulin resistance.
  
  
  METHODS
  MAFB mRNA expression was evaluated in human WAT from seven cohorts with large inter-individual variation in BMI and metabolic features. Insulin-induced adipocyte lipogenesis and lipolysis were measured and correlated with MAFB expression. MAFB regulation during adipogenesis and the effects of MAFB suppression in human adipocytes was investigated. MAFB regulation by TNF-α was examined in human primary adipocytes and THP-1 monocytes/macrophages.
  
  
  RESULTS
  MAFB expression in human adipocytes is upregulated during adipogenesis, increases with BMI in WAT, correlates with adverse metabolic features and is decreased after weight loss. MAFB downregulation decreases proinflammatory gene expression in adipocytes and interferes with TNF-α effects. Interestingly, MAFB is differentially regulated by TNF-α in adipocytes (suppressed) and THP-1 cells (upregulated). Further, MAFB is primarily expressed in WAT macrophages/monocytes and its expression correlates with macrophage and inflammatory markers.
  
  
  CONCLUSIONS
  Our findings indicate that MAFB is a regulator and a marker of adipose tissue inflammation, a process that subsequently causes insulin resistance.
authors.affiliation: Department of Medicine Huddinge, Lipid laboratory, Karolinska Institutet, Novum, NVS D4, Hälsovägen 7, 14186, Stockholm, Sweden.
authors.forename: Annie M L
authors.initials: AM
authors.lastname: Pettersson
authors.forename: Juan R
authors.initials: JR
authors.lastname: Acosta
authors.forename: Christel
authors.initials: C
authors.lastname: Björk
authors.forename: Johan
authors.initials: J
authors.lastname: Krätzel
authors.forename: Britta
authors.initials: B
authors.lastname: Stenson
authors.forename: Lennart
authors.initials: L
authors.lastname: Blomqvist
authors.forename: Nathalie
authors.initials: N
authors.lastname: Viguerie
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.forename: Jurga
authors.initials: J
authors.lastname: Laurencikiene
mesh_terms: D017667:Adipocytes / Q000166:cytology; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000473:pathology; D015992:Body Mass Index; D002454:Cell Differentiation; D015331:Cohort Studies; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance; D050155:Lipogenesis; D008066:Lipolysis; D008264:Macrophages / Q000166:cytology; D051258:MafB Transcription Factor / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology; D009000:Monocytes / Q000166:cytology; D009765:Obesity / Q000378:metabolism; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C490407:MAFB protein, human; D051258:MafB Transcription Factor; D014409:Tumor Necrosis Factor-alpha