The Bile Acid Signaling Axis: Deciphering the Roles of FXR and TGR5 in Hepatic Steatosis, Fibrosis, and Cancer

Bile acids (BAs) serve not only as emulsifiers for lipid digestion but also as essential signaling molecules, governing various physiological and pathological processes through their interaction with the farnesoid X receptor (FXR) and the takeda G protein-coupled receptor 5 (TGR5). In recent years, the critical roles of FXR and TGR5 in ameliorating hepatic steatosis, modulating inflammatory responses, and regulating glucose and lipid metabolism, as well as in cholestasis, have gained significant recognition, positioning them as pivotal targets in liver disease research. This article offers a comprehensive review of the structural characteristics and physiological functions of both FXR and TGR5, highlighting their integral contributions to the pathogenesis and progression of various liver diseases, including metabolic dysfunction-associated steatotic liver disease (MASLD), cholestatic liver disease (CLD), liver fibrosis, and liver cancer. Additionally, it examines the latest advancements in the research and development of pharmacological agents targeting FXR and TGR5, encompassing both agonists and antagonists, and explores their potential clinical applications. A thorough understanding of the FXR and TGR5 signaling pathways will provide a critical theoretical foundation for the development of treatment strategies for liver diseases.