title: Potential Regulators Driving the Transition in Nonalcoholic Fatty Liver Disease: a Stage-Based View.
abstract: OBJECTIVE
  The incidence of nonalcoholic fatty liver disease (NAFLD), ranging from mild steatosis to hepatocellular injury and inflammation, increases with the rise of obesity. However, the implications of transcription factors network in progressive NAFLD remain to be determined.
  
  
  METHODS
  A co-regulatory network approach by combining gene expression and transcription influence was utilized to dissect transcriptional regulators in different NAFLD stages. In vivo, mice models of NAFLD were used to investigate whether dysregulated expression be undertaken by transcriptional regulators.
  
  
  RESULTS
  Through constructing a large-scale co-regulatory network, sample-specific regulator activity was estimated. The combinations of active regulators that drive the progression of NAFLD were identified. Next, top regulators in each stage of NAFLD were determined, and the results were validated using the different experiments and bariatric surgical samples. In particular, Adipocyte enhancer-binding protein 1 (AEBP1) showed increased transcription activity in nonalcoholic steatohepatitis (NASH). Further characterization of the AEBP1 related transcription program defined its co-regulators, targeted genes, and functional organization. The dynamics of AEBP1 and its potential targets were verified in an animal model of NAFLD.
  
  
  CONCLUSIONS
  This study identifies putative functions for several transcription factors in the pathogenesis of NAFLD and may thus point to potential targets for therapeutic interventions.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lou
authors.forename: Yi-Dan
authors.initials: YD
authors.lastname: Chen
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Sun
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Shi
authors.forename: Yu
authors.initials: Y
authors.lastname: Song
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D002268:Carboxypeptidases / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D053263:Gene Regulatory Networks; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000473:pathology*; D012097:Repressor Proteins / Q000378:metabolism; D012720:Severity of Illness Index; D059467:Transcriptome
chemical_list: C112918:Aebp1 protein, mouse; D001057:Apolipoproteins E; D012097:Repressor Proteins; D002268:Carboxypeptidases
keywords: NAFLD; Network; Transcription factor