title: The role of apolipoprotein A5 in non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Apolipoprotein A5 (apoA5) is a recently described liver-specific protein that has been shown to influence triglyceride (TG) metabolism. ApoA5 transgenic mice display dramatically reduced TG levels, while in contrast apoA5 deficiency in humans was reported to result in marked hypertriglyceridemia. ApoA5 exerts its extracellular effects by increasing lipolysis of TG-rich lipoproteins, while in vitro data suggest additional intrahepatic effects.
  
  
  METHODS
  In this study the authors set out to investigate a possible role of apoA5 in non-alcoholic fatty liver disease (NAFLD). We thus determined hepatic apoA5 expression in 15 obese subjects with histologically proven NAFLD undergoing bariatric surgery. In addition, the authors established a hepatic cell culture model of apoA5 knockdown by transfecting human hepatoma cells (HepG2) with apoA5 small interfering (si) RNA, and determined intracellular TG content and expression levels of key enzymes and transcription factors of intrahepatic lipid metabolism in these cells.
  
  
  RESULTS
  Pronounced weight loss and associated histologically verified improvement of hepatic steatosis were accompanied by significant reductions of hepatic apoA5 mRNA expression levels. Significant apoA5 knockdown in HepG2 cells resulted in a marked decrease of intracellular TG content. When HepG2 cells were co-transfected with apoA5 and peroxisome proliferator-activated receptor gamma (PPARγ), reductions in hepatic TG accumulation were significantly less pronounced when compared to apoA5 siRNA transfected HepG2 cells.
  
  
  CONCLUSIONS
  In obese subjects, hepatic apoA5 mRNA expression decreases after weight loss and improvements in hepatic steatosis. The authors' in vitro data demonstrate that apoA5 influences intrahepatic TG metabolism and that these intracellular effects of apoA5 are accompanied by changes in PPARγ mRNA expression. In summary, the data suggest that as well as several other factors, apoA5 might be involved in the pathogenesis of hepatic steatosis.
authors.affiliation: Medical University Innsbruck, Department of Internal Medicine I, Innsbruck, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Ress
authors.forename: A R
authors.initials: AR
authors.lastname: Moschen
authors.forename: N
authors.initials: N
authors.lastname: Sausgruber
authors.forename: A
authors.initials: A
authors.lastname: Tschoner
authors.forename: I
authors.initials: I
authors.lastname: Graziadei
authors.forename: H
authors.initials: H
authors.lastname: Weiss
authors.forename: W
authors.initials: W
authors.lastname: Schgoer
authors.forename: C F
authors.initials: CF
authors.lastname: Ebenbichler
authors.forename: R J
authors.initials: RJ
authors.lastname: Konrad
authors.forename: J R
authors.initials: JR
authors.lastname: Patsch
authors.forename: H
authors.initials: H
authors.lastname: Tilg
authors.forename: S
authors.initials: S
authors.lastname: Kaser
mesh_terms: D000328:Adult; D000886:Anthropometry / Q000379:methods; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050110:Bariatric Surgery; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D055785:Gene Knockdown Techniques; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications / Q000378:metabolism / Q000601:surgery; D047495:PPAR gamma / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015431:Weight Loss / Q000502:physiology
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D047495:PPAR gamma; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D014280:Triglycerides