title: Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies.
abstract: OBJECTIVE
  Fetuin A has been associated with insulin resistance and the metabolic syndrome. We therefore explored the role of fetuin A in nonalcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  Cross-sectional and intervention studies.
  
  
  METHODS
  We included 111 subjects with histologically proven NAFLD of whom 44 participated in a randomized, controlled trial with metformin. One hundred and thirty-one healthy subjects and 13 subjects undergoing hepatic surgery for metastatic cancer served as controls. Main outcome variables were circulating levels of fetuin A according to the presence of NAFLD, hepatic gene expression of fetuin A and key enzymes in glucose and lipid metabolism, and the effect of metformin on fetuin A levels in vivo and in vitro (HepG2 cells).
  
  
  RESULTS
  Fetuin A levels were significantly higher in NAFLD patients compared with controls (324 ± 98 vs 225 ± 75 mg/l, P<0.001). NAFLD was a significant predictor of elevated fetuin A levels (β=174 (95% confidence interval: 110-234)) independent of body mass index, age, sex, fasting glucose, and triglycerides. Hepatic fetuin A mRNA levels correlated significantly with hepatic mRNA levels of key enzymes in lipid (sterol regulatory element-binding protein 1c, carnitine palmitoyltransferase 1) and glucose (phosphoenol pyruvate kinase 1, glucose-6-phosphatase) metabolism. Plasma fetuin A levels decreased significantly after metformin treatment compared with placebo (-40 ± 47 vs 15 ± 82 mg/l, P = 0.008). Metformin induced a dose-dependent decrease in fetuin A secretion in vitro.
  
  
  CONCLUSIONS
  Fetuin A levels were elevated in NAFLD. Hepatic expression of fetuin A correlated with key enzymes in glucose and lipid metabolism. Metformin decreased fetuin A levels in vitro.
authors.affiliation: Department of Gastroenterology Research Institute for Internal Medicine, Oslo University Hospital Ullevål, PB 4950, 0424 Oslo, Norway. j.w.haukeland@medisin.uio.no
authors.forename: John Willy
authors.initials: JW
authors.lastname: Haukeland
authors.forename: Tuva B
authors.initials: TB
authors.lastname: Dahl
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: Ivar P
authors.initials: IP
authors.lastname: Gladhaug
authors.forename: Else Marit
authors.initials: EM
authors.lastname: Løberg
authors.forename: Terese
authors.initials: T
authors.lastname: Haaland
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Konopski
authors.forename: Cecilie
authors.initials: C
authors.lastname: Wium
authors.forename: Erlend T
authors.initials: ET
authors.lastname: Aasheim
authors.forename: Odd Erik
authors.initials: OE
authors.lastname: Johansen
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Kåre I
authors.initials: KI
authors.lastname: Birkeland
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism* / Q000601:surgery; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary / Q000601:surgery; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D060749:alpha-2-HS-Glycoprotein / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: C556354:AHSG protein, human; D015415:Biomarkers; D060749:alpha-2-HS-Glycoprotein; D008687:Metformin