Role of Activin A as a novel marker for diagnosis and evaluation of nonalchoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a disease gaining increasing interest worldwide. It ranges from simple nonalcoholic steatosis to nonalcoholic steatohepatitis (NASH), is characterized by steatosis, inflammation and fibrosis, and may lead to liver cirrhosis and hepatocellular carcinoma. Nonalcoholic fatty liver disease shares common pathogenetic mechanisms with other components of the insulin resistance or metabolic syndrome, with adipokines playing a crucial role. The prevalence of Nonalcoholic fatty liver disease increases in parallel with the epidemics of obesity and type 2 diabetes mellitus. non-alcoholic steatohepatitis diagnosis requires liver biopsy, an invasive method, thereby developing noninvasive markers for Nonalcoholic fatty liver disease represents a field of extensive research, targeting to replace liver biopsy or identify candidates for liver biopsy. Furthermore, despite the high prevalence of the disease, Nonalcoholic fatty liver disease treatment remains an unmet medical need. Activin A is a member of the tumor growth factor (TGF)-β superfamily and is regarded as a multifunctional cytokine expressed in a wide range of tissues and cells, where it regulates cellular differentiation, homeostasis of cell number and tissue architecture, inflammation, cell proliferation and apoptosis. In hepatocytes, a complex role has been attributed to activin A; it is reported to be beneficial against lipid accumulation, but it may promote hepatic inflammation and fibrosis. It enhances the expression of collagen and TGF-β1, induces mitochondrial β-oxidation, down-regulates fatty acid synthase activity, promotes decreased weight percentage of saturated fatty acids, alters the composition of polyunsaturated fatty acids and promotes matrix metalloproteinase activity. Its expression is elevated