A complex role of activin A in non-alcoholic fatty liver disease
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.
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Serum levels of FST are significantly increased in individuals with NAFLD.
“serum levels of FST are also significantly increased in individuals with NAFLD [193].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [193]
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- Authors
- Yndestad, A., Haukeland, J. W., Dahl, T. B., Bjøro, K., Gladhaug, I. P., Berge, C., Damås, J. K., Haaland, T., Løberg, E. M., Linnestad, P., Birkeland, K., Konopski, Z., Halvorsen, B., Berge, R. K., & Aukrust, P.
- Affiliations
- Oslo University Hospital (NO)
- Haukeland University Hospital (NO)
- Corresponding author
- Yndestad, Arne
- ORCID
- Venue
- The American Journal of Gastroenterology
- Published
- 2009-06-16
- Volume
- 104
- Issue
- 9
- Pages
- 2196-2205
- ISSN
- 0002-9270 (ISSN-L)
- 1572-0241
- OpenAlex
- W1970984455
- Cited by
- 75
- References
- 44
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 6 · 2023: 8 · 2022: 10 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 9 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 2
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- activin A, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, follistatin, liver fibrosis, TGF-β1, collagen expression, matrix metalloproteinases, fatty acid synthase, mitochondrial beta-oxidation, fatty acid composition, hepatocytes, hepatic lipid accumulation
- MeSH terms
- Adult, Fatty Liver, Female, Humans, Liver Cirrhosis, Male, Middle Aged, Gene Expression, Activins, Follistatin, Cell Line, Tumor
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