title: Adipocytokine expression associated with miRNA regulation and diagnosis of NASH in obese patients with NAFLD.
abstract: OBJECTIVE
  Non-alcoholic fatty liver disease (NAFLD) is strongly associated with visceral adiposity. The secretion of adipocytokines from white adipose tissue (WAT) promoting necroinflammation, and/or fibrosis may play important roles in the pathogenesis of non-alcoholic steatohepatits (NASH). In a previous study, reduced expression of a number of miRNA species in WAT concomitant with histological diagnosis of NASH was successfully demonstrated. In this study, we measure the expression of several predicted miRNA regulatory targets relevant to NAFLD and NASH including mTOR, FAS, IL20, SEMA4C, ADAMTS6 and IL13RA. We then examine hepatic receptor expression by immunohistochemical staining and qPCR.
  
  
  METHODS
  White adipose tissue was collected from 24 obese patients undergoing bariatric surgery with biopsy-proven NAFLD. Extracted total RNAs from the adipose tissue were reverse transcribed and profiled for gene expression by qPCR for specific individual mRNA targets defined after identification by any two of three of the major prediction services: miRanda, TarBase or PicTar. All liver biopsies were read by a singly hepatopathologist. The same liver tissue was used to stain for hepatic receptor expression for FASLG and IL20. Additionally, the same tissue was used for qPCR for FASLG and IL20.
  
  
  RESULTS
  Increases in the expression of IL13RA, mTOR, IL20, SEMA4C and FAS were detected and negatively correlated with putative regulatory miRNA. Hepatic receptor expression for FAS and IL20 was noted to correlate with markers of inflammation and severity of NAFLD.
  
  
  CONCLUSIONS
  These data are consistent with the hypothesis that specific adipocytokines secreted by WAT will impact hepatic tissue and participate in the pathogenesis of NASH.
authors.affiliation: Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
authors.forename: J Michael
authors.initials: JM
authors.lastname: Estep
authors.forename: Zachary
authors.initials: Z
authors.lastname: Goodman
authors.forename: Haveesh
authors.initials: H
authors.lastname: Sharma
authors.forename: Elana
authors.initials: E
authors.lastname: Younossi
authors.forename: Hazem
authors.initials: H
authors.lastname: Elarainy
authors.forename: Ancha
authors.initials: A
authors.lastname: Baranova
authors.forename: Zobair
authors.initials: Z
authors.lastname: Younossi
mesh_terms: D054392:Adipokines / Q000235:genetics*; D052436:Adipose Tissue, White / Q000737:chemistry*; D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D008099:Liver / Q000737:chemistry* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000235:genetics*; D009765:Obesity / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D019899:Paracrine Communication; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D015398:Signal Transduction; D019014:fas Receptor / Q000235:genetics
chemical_list: D054392:Adipokines; C491901:FAS protein, human; D018836:Inflammation Mediators; D035683:MicroRNAs; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019014:fas Receptor; C492510:interleukin-20 receptor
keywords: FAS; NAFLD; NASH; miRNA; obesity