Journal
AMERICAN JOURNAL OF GASTROENTEROLOGY
Volume 104, Issue 9, Pages 2196-2205Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ajg.2009.318
Keywords
-
Categories
Funding
- Norwegian Research Council
- University of Oslo
- Medinnova Foundation
- Helse Sor
- Rikshospitalet University Hospital
- NCoE Centre
- MitoHealth
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [K24DK081913] Funding Source: NIH RePORTER
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available