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

Abstract

Our findings support the complex role of activin A in the pathogenesis of NAFLD, involving effects on fibrosis and lipid accumulation.

Inhibiting myostatin reverses muscle fibrosis through apoptosis

“…While these results indicate that ActRIIB.mFc acts to reverse fibrosis through the inhibition of myostatin, they do not exclude the possibility that ActRIIB.mFc's antifibrotic action is enhanced by inhibition of activins and GDF11 to which it has also been shown to bind (Morrison et al, 2009;Sako et al, 2010). Activins are widely expressed and have been implicated in fibrosis of multiple organs including liver and kidney among others (Yndestad et al, 2009;Wada et al, 2004;Werner et al, 2006;Ren et al, 2009). GDF11 shares 90% amino acid identity with myostatin and has a similar signaling pathway (McPherron et al, 1999).…”

Circulating Follistatin Is Liver-Derived and Regulated by the Glucagon-to-Insulin Ratio

“…Alternatively, follistatin may act to increase ␤-cell mass as a compensatory mechanism to combat increasing blood glucose. Circulating follistatin is also elevated in patients with NAFLD and NASH (10). Interestingly, follistatin 315-deletion in mice results in hepatic steatosis associated with increased hepatic gene expression of low-density lipoprotein receptor, lipoprotein lipase, acetyl-CoA carboxylase 1, and fatty acid synthase, suggestive of increased lipid uptake and de novo lipogenesis in these mice (48).…”

“…In addition, follistatin has been linked to metabolic diseases because it is elevated in plasma in patients with type 2 diabetes (9), nonalcoholic fatty liver disease (NAFLD) (10), and nonalcoholic steatohepatitis (NASH) (10). Follistatin is expressed in a broad range of cells, but no specific tissue or organ is identified as the source of circulating follistatin.…”

Circulating activin A is a novel prognostic biomarker in malignant pleural mesothelioma – A multi-institutional study

“…Activin A and its receptors are critically involved in cellular differentiation, homoeostasis and tissue architecture in multiple organs [6]. Furthermore, the deregulation of activin A signalling has been linked to non-malignant diseases including asthma [7], chronic obstructive pulmonary disease [8], osteoporosis [9] and liver cirrhosis [10]. While in cancers of the breast, liver and colon, activin signals were found to inhibit tumour cell growth, and tumour tissue expressed decreased levels of activin A [11e14], in thoracic malignancies, including lung and oesophageal adenocarcinoma, increased activin A expression was associated with tumour cell aggressiveness [15e17].…”