title: Meta-analysis reveals up-regulation of cholesterol processes in non-alcoholic and down-regulation in alcoholic fatty liver disease.
abstract: OBJECTIVE
  To compare transcriptomes of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) in a meta-analysis of liver biopsies.
  
  
  METHODS
  Employing transcriptome data from patient liver biopsies retrieved from several public repositories we performed a meta-analysis comparing ALD and NAFLD.
  
  
  RESULTS
  We observed predominating commonalities at the transcriptome level between ALD and NAFLD, most prominently numerous down-regulated metabolic pathways and cytochrome-related pathways and a few up-regulated pathways which include ECM-receptor interaction, phagosome and lysosome. However some pathways were regulated in opposite directions in ALD and NAFLD, for example, glycolysis was down-regulated in ALD and up-regulated in NAFLD. Interestingly, we found rate-limiting genes such asHMGCR,SQLEandCYP7A1which are associated with cholesterol processes adversely regulated between ALD (down-regulated) and NAFLD (up-regulated). We propose that similar phenotypes in both diseases may be due to a lower level of the enzyme CYP7A1 compared to the cholesterol synthesis enzymes HMGCR and SQLE. Additionally, we provide a compendium of comparative KEGG pathways regulation in ALD and NAFLD.
  
  
  CONCLUSIONS
  Our finding of adversely regulated cholesterol processes in ALD and NAFLD draws the focus to regulation of cholesterol secretion into bile. Thus, it will be interesting to further investigate CYP7A1-mediated cholesterol secretion into bile - also as possible drug targets. The list of potential novel biomarkers may assist differential diagnosis of ALD and NAFLD.
authors.affiliation: Wasco Wruck, James Adjaye, Medical Faculty, Institute for Stem Cell Research and Regenerative Medicine, Heinrich Heine University, 40225 Düsseldorf, Germany.
authors.forename: Wasco
authors.initials: W
authors.lastname: Wruck
authors.affiliation: Wasco Wruck, James Adjaye, Medical Faculty, Institute for Stem Cell Research and Regenerative Medicine, Heinrich Heine University, 40225 Düsseldorf, Germany.
authors.forename: James
authors.initials: J
authors.lastname: Adjaye
keywords: Alcohol dehydrogenase; Alcoholic liver disease cholesterol; Bile; CYP7A1; Non-alcoholic fatty liver disease