Biological functions and pharmacological behaviors of bile acids in metabolic diseases
Tongxi Zhuang, Xunjiang Wang, Zixuan Wang, Lihua Gu, Dawei Yue, Zhengtao Wang, Xiaohua Li, Li Yang, Wendong Huang, Lili Ding
Abstract
• Functional bile acids (BAs) demonstrate diverse pharmacological activities attributed to their unique structural variations. • BA receptors mediate essential signaling pathways that regulate glucose and lipid metabolism, and immune responses, crucial for maintaining metabolic balance. • BAs hold significant potential in safeguarding metabolic homeostasis and organ function through activation of the TGR5 and FXR signaling pathways. • Recently discovered BA- or BA analog-based medications offer promising approaches for addressing a spectrum of metabolic and gastrointestinal disorders, showcasing the therapeutic versatility of BAs. Bile acids (BAs), synthesized endogenously from cholesterol, play a central role in metabolic regulation within the enterohepatic circulatory system. Traditionally known as emulsifying agents that facilitate the intestinal absorption of vitamins and lipids, recent research reveals their function as multifaceted signal modulators involved in various physiological processes. These molecules are now recognized as key regulators of chronic metabolic diseases and immune dysfunction. Despite progress in understanding their roles, their structural diversity and the specific functions of individual bile acids remain underexplored. This study categorizes the bile acids based on their chemical structures and their roles as signaling molecules in physiological processes. It consolidates current knowledge and provides a comprehensive overview of the current research. The review also includes natural and semisynthetic variants that have demonstrated potential in regulating metabolic processes in animal models or clinical contexts. Bile acids circulate primarily within the enterohepatic circulation, where they help maintain a healthy digestive system. Disruptions in their balance are linked to metabolic disorders, hepatobiliary diseases and intestinal inflammation. Through receptor-mediated pathways, bile acids influence the progression of metabolic diseases by regulating glucose and lipid metabolism, immune function, and energy expenditure. This review aims to provide a comprehensive, systematic foundation to for understanding their physiological roles and supporting future therapeutic developments for metabolic and inflammatory diseases.