title: A complex role of activin A in non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  Recent studies suggest that activin A, a member of the transforming growth factor (TGF) superfamily, is involved in the pathogenesis of liver disorders. We sought to explore its possible role in non-alcoholic fatty liver disease (NAFLD).
  
  
  METHODS
  Serum levels of activin A and its natural inhibitor, follistatin, were measured in patients with NAFLD (n=70) and in control subjects (n=30). Gene expression was quantified in liver biopsies obtained from patients with NAFLD (n=13) and controls (n=6). Effects of activin A were examined in Huh7 (human hepatoma cell line) hepatocytes.
  
  
  RESULTS
  Patients with NAFLD had significantly elevated serum levels of activin A and follistatin compared with healthy controls. In patients with non-alcoholic steatohepatitis (NASH, n=38), there were particularly high levels of activin A that were significantly related to the degree of hepatic fibrosis. Liver biopsies from NAFLD patients showed a markedly increased activin A-follistatin mRNA ratio, indicating increased hepatic activin A activity. In hepatocytes, activin A enhanced the expression of collagen and TGF-beta(1), promoted matrix metalloproteinase activity, induced mitochondrial beta-oxidation, downregulated fatty acid (FA) synthase activity, promoted decreased weight percentage of saturated FAs, and altered the composition of polyunsaturated FAs.
  
  
  CONCLUSIONS
  Our findings support the complex role of activin A in the pathogenesis of NAFLD, involving effects on fibrosis and lipid accumulation.
authors.affiliation: Research Institute for Internal Medicine, Rikshospitalet, Oslo University Hospital, Oslo, N-0027, Norway. arne.yndestad@rr-research.no
authors.forename: Arne
authors.initials: A
authors.lastname: Yndestad
authors.forename: John Willy
authors.initials: JW
authors.lastname: Haukeland
authors.forename: Tuva Børresdatter
authors.initials: TB
authors.lastname: Dahl
authors.forename: Kristian
authors.initials: K
authors.lastname: Bjøro
authors.forename: Ivar Prydz
authors.initials: IP
authors.lastname: Gladhaug
authors.forename: Christ
authors.initials: C
authors.lastname: Berge
authors.forename: Jan Kristian
authors.initials: JK
authors.lastname: Damås
authors.forename: Terese
authors.initials: T
authors.lastname: Haaland
authors.forename: Else Marit
authors.initials: EM
authors.lastname: Løberg
authors.forename: Paul
authors.initials: P
authors.lastname: Linnestad
authors.forename: Kåre
authors.initials: K
authors.lastname: Birkeland
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Konopski
authors.forename: Bente
authors.initials: B
authors.lastname: Halvorsen
authors.forename: Rolf Kristian
authors.initials: RK
authors.lastname: Berge
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
mesh_terms: D028341:Activins / Q000097:blood* / Q000378:metabolism; D000328:Adult; D045744:Cell Line, Tumor; D005234:Fatty Liver / Q000097:blood* / Q000503:physiopathology; D005260:Female; D038681:Follistatin / Q000097:blood* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged
chemical_list: D038681:Follistatin; C422405:activin A; D028341:Activins