Nuclear receptors and transcriptional regulation in non-alcoholic fatty liver disease

Abstract Background As a result of a sedentary lifestyle and excess food consumption in modern society, non-alcoholic fatty liver disease (NAFLD) characterized by fat accumulation in the liver is becoming a major disease burden. Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD, characterized by inflammation and fibrosis which can lead to hepatocellular carcinoma and liver failure. Nuclear receptors (NRs) are a family of ligand-regulated transcription factors which closely control multiple aspects of metabolism, and their transcriptional activity is modulated by various ligands, including hormones and lipids. Thus, NRs serve as potential pharmacological targets for NAFLD/NASH and other metabolic diseases. Scope of Review In this review, we provide a comprehensive overview of NRs that have been studied in the context of NAFLD/NASH with a focus on their transcriptional regulation, function in pre-clinical models, and studies of their clinical utility. Major Conclusions The transcriptional regulation of NRs is context-dependent. During the dynamic progression of NAFLD/NASH, NRs play diverse roles in multiple organs and different cell types in the liver, which highlights the necessity of targeting NRs in a stage-specific and cell-type specific manner to enhance the efficacy and safety of treatment methods.