The Role of Bile Acid Receptors in Non-alcoholic Fatty Liver Disease (NAFLD) / 中国生物化学与分子生物学报

ABSTRACT

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease and its incidence is increasing year by year worldwide. Insulin resistance and derangement of lipid metabolism, accompanied by activation of the pro-inflammatory response and fibrosis, play an important role in its occurrence and development. However, the understanding of NAFLD is still very poor, and there is still a lack of effective drugs in clinical practice. Researchers are trying to explore the etiology of NAFLD and a new breakthrough in its treatment. Bile acid is one of the many metabolites synthesized in the liver. In addition to helping fat digestion and absorption, bile acid also acts as a signal molecule to activate the bile acid receptor, which is an important transcriptional regulatory factor and plays an important role in maintaining normal physiological metabolism of the body. More and more evidence shows that the function of the bile acid receptor is closely related to the occurrence of NAFLD, and the study of its related roles and functions can provide new insights and drug therapeutic targets for the treatment of NAFLD. Bile acid receptors include nuclear receptors, such as farnesoid X receptor (FXR), pregnane X receptor (PXR), etc., and cell surface receptors, such as transmembrane G protein-coupled receptor 5 (TGR5), sphingosine-1-phosphate receptor 2 (S1PR2) and M3 muscarinic receptor. In this review, we summarize the research progress on the role of bile acid receptors in the pathogenesis of NAFLD by regulating bile acid homeostasis, lipid and glucose metabolism, energy metabolism, liver inflammation and fibrosis, and we further elaborated on the current status of bile acid receptor agonists in the treatment of NAFLD, in order to have a more comprehensive understanding of the pathogenesis of NAFLD and find a more effective way of treatment.