Is Nrf2-ARE a potential target in NAFLD mitigation?

Nonalcoholic fatty liver disease (NAFLD) is defined as a metabolic syndrome associated with obesity and type 2 diabetes mellitus (T2DM) and characterized as excessive triglyceride accumulation in 5% or more of the hepatocyte population without significant alcohol consumption. Although the worldwide prevalence of NAFLD is increasing, except dietary control, there remains no effective treatment to improve NAFLD clinically. Nuclear factor erythroid-derived 2-like 2 (NFE2L2, also known as Nrf2) is one of the most important transcription factors in regulating adaptive antioxidants and xenobiotic stress responses. Recently, a variety of studies have started to investigate the potential involvement of Nrf2 in the development of NAFLD and to utilize Nrf2 activators in an attempt to ameliorate hepatic steatosis and inflammation. However, the results are, so far, controversial and complex. This review attempts to highlight the hypothetical roles of Nrf2 in the incidence of NAFLD. In addition, we provide recommendations on therapeutic strategies of Nrf2 activators in NAFLD, including use in the proper phase of the disease for the greatest impact.