ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) denotes a spectrum of fatty liver disease in individuals without significant alcohol consumption. NAFLD is set to be the most common etiology of serious liver diseases in numerous nations when accompanied by obesity and type 2 diabetes. It is further histologically categorized into the non-alcoholic fatty liver (NAFL; steatosis without hepatocellular injury) and non-alcoholic steatohepatitis (NASH) which is characterized by the coexistence of hepatic steatosis and inflammation and is accompanied by hepatocyte injury (ballooning), either with or without fibrosis. NAFL is considered the benign and reversible stage arising from the excessive accumulation of triglycerides in hepatocytes. However, NASH is a more progressive stage of NAFLD, due to the increased risks of evolving more serious diseases such as cirrhosis, hepatocellular carcinoma. This concept, however, has been lately challenged by a hypothesis of multiple parallel hits of NAFLD, in which steatosis and NASH are separate entities rather than two points of the NAFLD spectrum, not only from a set of histological patterns but also from a pathophysiological perspective. The current review highlights the epidemiology and pathophysiology of NAFLD, and its progression towards steatohepatitis, with special focus on the novel imminent therapeutic approaches targeting the molecular aspects and the pathogenic pathways involved in the development, and progression of NAFLD.
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.