A complex role of activin A in non-alcoholic fatty liver disease.
Am J Gastroenterol
; 104(9): 2196-205, 2009 Sep.
Article
em En
| MEDLINE
| ID: mdl-19532130
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-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativinas
/
Folistatina
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Fígado Gorduroso
/
Cirrose Hepática
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Gastroenterol
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Noruega