Implications for Farnesoid X Receptor Signaling on Bile Acid Metabolism as a Potential Therapeutic Strategy for Nonalcoholic Fatty Liver Disease

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in both developed and developing countries and is an important risk factor for both hepatic and cardiometabolic mortality. Despite decades of clinical trials, effective treatment options for NAFLD are limited, requiring novel therapeutic approaches to prevent disease development and progression to cirrhosis and cancer. Recently, bile acids have emerged as signaling molecules and metabolic regulators that can activate signaling mediated by nuclear receptors and G protein-coupled receptors to regulate hepatic lipid, glucose, and energy homeostasis, as well as its own synthesis and transport in the liver and intestine. Many recent studies have reported that the activation or modulation of bile acid signaling mediated by bile acid receptors favorably affects both insulin sensitivity and NAFLD pathogenesis at multiple levels, suggesting that these approaches hold promise as novel therapies. In this review, we provide an overview of the role of bile acids, in particular, their signaling related to the nuclear receptor farnesoid X receptor in NAFLD and new insights into the possible approach of targeting bile acid-related pathways in the treatment of this serious disease.