Activin A in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is emerging as one of the most common causes of abnormal liver function. NAFLD is a spectrum of disease ranging from simple steatosis (i.e., fat accumulation) of the liver to nonalcoholic steatohepatitis (NASH) with inflammation and fibrosis. NAFLD involves the accumulation of triglycerides in hepatocytes, necrosis, and apoptosis of these cells, accompanied by inflammatory and fibrogenic responses within the liver, potentially leading to the development of cirrhosis. Activin A, a member of the transforming growth factor-β family of cytokines, has been recognized as a multifunctional cytokine expressed in a wide range of cells and tissues with roles in regulation of wound repair, cell differentiation, apoptosis, and inflammation. Growing evidence suggests that activin A could be involved in the pathogenesis of various liver disorders such as acute liver injury, chronic viral hepatitis, and certain hepatic malignancies, and recently we demonstrated an involvement of activin A in NAFLD. In this chapter, after a general introduction to NAFLD and activin A biology, we elaborate a potential pathogenic role of activin A in the development and progression of NAFLD.