Bile acids and metabolic syndrome

Bile acids (BAs) are not only facilitators of dietary lipid absorption but also important signaling molecules that participate in various metabolic pathways. Some major signaling pathways involving the nuclear BAs receptor farnesoid X receptor (FXR) and the G protein-coupled BAs receptor TGR5/M-BAR have been identified to be the targets of BAs. BAs affect diverse metabolic pathways including glucose metabolism, lipid metabolism, and energy expenditure via these major pathways. Therefore, BA signaling mechanisms are attractive therapeutic targets of the metabolic syndrome. Actually, bile acid-binding resin (BABR) originally used to treat hypercholesterolemia also stimulates incretin secretion and improves glucose metabolism. In addition to BABR, the clinical applications of FXR and TGR5/M-BAR agonists are ongoing for the treatment of metabolic syndrome. The effects of bariatric surgery on glycemic control are also associated with BA metabolism. In this chapter, we summarize current knowledge of the metabolic regulation mechanisms of BAs and propose BA signaling pathways as a therapeutic target of the metabolic syndrome.