TITLE

A Complex Role of Activin A in Non-Alcoholic Fatty Liver Disease

AUTHOR(S)
Yndestad, Arne; Haukeland, John Willy; Dahl, Tuva Børresdatter; Bjøro, Kristian; Gladhaug, Ivar Prydz; Berge, Christ; Damås, Jan Kristian; Haaland, Terese; Løberg, Else Marit; Linnestad, Paul; Birkeland, Kåre; Konopski, Zbigniew; Halvorsen, Bente; Berge, Rolf Kristian; Aukrust, Pål
PUB. DATE
September 2009
SOURCE
American Journal of Gastroenterology;Sep2009, Vol. 104 Issue 9, p2196
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
OBJECTIVES: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-β1, promoted matrix metalloproteinase activity, induced mitochondrial β-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.
ACCESSION #
44012439

 

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