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

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
September 2009
American Journal of Gastroenterology;Sep2009, Vol. 104 Issue 9, p2196
Academic Journal
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.


Related Articles

  • Activin A expression regulates multipotency of mesenchymal progenitor cells. Djouad, Farida; Jackson, Wesley M.; Bobick, Brent E.; Janjanin, Sasa; Yingjie Song; Huang, George T. J.; Tuan, Rocky S. // Stem Cell Research & Therapy;2010, Vol. 1 Issue 2, p1 

    Introduction: Bone marrow (BM) stroma currently represents the most common and investigated source of mesenchymal progenitor cells (MPCs); however, comparable adult progenitor or stem cells have also been isolated from a wide variety of tissues. This study aims to assess the functional...

  • Structural basis for the inhibition of activin signalling by follistatin. Harrington, Adrian E.; Morris-Triggs, Samantha A.; Ruotolo, Brandon T.; Robinson, Carol V.; Ohnuma, Shin-ichi; Hyvönen, Marko // EMBO Journal;3/8/2006, Vol. 25 Issue 5, p1035 

    The secreted, multidomain protein follistatin binds activins with high affinity, inhibiting their receptor interaction. We have dissected follistatin's domain structure and shown that the minimal activin-inhibiting fragment of follistatin is comprised of the first and second Fs domains (Fs12)....

  • AT1 antagonist modulates activin-like kinase 5 and TGF-β receptor II in the developing kidney. Yim, Hyung; Kim, Mee; Bae, In; Kim, Ji; Choi, Byung; Yoo, Kee; Hong, Young; Lee, Joo // Pediatric Nephrology;Oct2006, Vol. 21 Issue 10, p1377 

    Previous studies by our group have demonstrated that angiotensin-converting enzyme (ACE) inhibition in the developing kidney modulates transforming growth factor-β receptors. Blocking of angiotensin II (ANG II) mainly through angiotensin II type 1 receptor (AT1) has been implicated in...

  • Activin A/BMP2 chimera AB235 drives efficient redifferentiation of long term cultured autologous chondrocytes. Jiménez, G.; López-Ruiz, E.; Kwiatkowski, W.; Montañez, E.; Arrebola, F.; Carrillo, E.; Gray, P. C.; Belmonte, J. C. Izpisua; Choe, S.; Perán, M.; Marchal, J. A. // Scientific Reports;11/13/2015, p16400 

    Autologous chondrocyte implantation (ACI) depends on the quality and quantity of implanted cells and is hindered by the fact that chondrocytes cultured for long periods of time undergo dedifferentiation. Here we have developed a reproducible and efficient chondrogenic protocol to redifferentiate...

  • Genomic organization and mapping of the human activin receptor type IIB (hActR-IIB) gene. Ishikawa, Shinji; Kai, Mikio; Murata, Yasushi; Tamari, Mayumi; Daigo, Yataro; Murano, Takeshi; Ogawa, Michio; Nakamura, Y. // Journal of Human Genetics;1998, Vol. 43 Issue 2, p132 

    Abstract Activins, members of a family of proteins that includes transforming growth factor-beta (TGF-beta), are gonadal polypeptide hormones that stimulate secretion of follicle-stimulating hormone (FSH). During large-scale sequencing analysis of a 1.2-Mb fragment of human genomic DNA on...

  • Obesity, Visceral Fat, and NAFLD: Querying the Role of Adipokines in the Progression of Nonalcoholic Fatty Liver Disease. Mirza, M. S. // ISRN Gastroenterology;2011, Special section p1 

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of clinicopathologic conditions ranging from steatosis alone to nonalcoholic steatohepatitis (NASH), with varying risks for progression to cirrhosis and hepatocellular carcinoma. There is mounting evidence that NAFLD not only...

  • CD44 Upregulation in E-Cadherin-Negative Esophageal Cancers Results in Cell Invasion. Bras, Grégoire F. Le; Allison, Gillian L.; Richards, Nicole F.; Ansari, Shazia S.; Washington, M. Kay; Claudia D. Andl // PLoS ONE;2011, Vol. 6 Issue 11, p1 

    E-cadherin is frequently lost during epithelial-mesenchymal transition and the progression of epithelial tumorigenesis. We found a marker of epithelial-mesenchymal transition, CD44, upregulated in response to functional loss of E-cadherin in esophageal cell lines and cancer. Loss of E-cadherin...

  • Pancreatic Transcription Factors Containing Protein Transduction Domains Drive Mouse Embryonic Stem Cells towards Endocrine Pancreas. Lima, Maria João; Docherty, Hilary M.; Chen, Yuanxiao; Vallier, Ludovic; Docherty, Kevin // PLoS ONE;May2012, Vol. 7 Issue 5, p1 

    Protein transduction domains (PTDs), such as the HIV1-TAT peptide, have been previously used to promote the uptake of proteins into a range of cell types, including stem cells. Here we generated pancreatic transcription factors containing PTD sequences and administered these to endoderm enriched...

  • Serum transforming growth factor beta 3 predicts future development of nonalcoholic fatty liver disease. Yongli Wei; Qing Tian; Xiuxia Zhao; Xingchun Wang // International Journal of Clinical & Experimental Medicine;2015, Vol. 8 Issue 3, p4545 

    Transforming growth factor beta 3 (TGFb3) was mainly expressed by liver satellite cells in the normal liver, but it may be expressed by various liver cells during liver diseases, e.g. hepatitis and cirrhosis. However, whether TGFb3 level may be used to predict development of nonalcoholic fatty...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics