Bile acid signaling

"Bile acid signaling" does not refer to a single molecule or canonical drug target but rather encompasses the complex network of biological processes initiated when **bile acids** bind their principal receptors—primarily the **Farnesoid X receptor** (*FXR*, NR1H4) and the **G protein-coupled bile acid receptor 1** (*TGR5*, GPBAR1). These steroid-derived molecules are synthesized from cholesterol in the liver, modified by gut microbiota into secondary forms, then act both locally and systemically. Through their interaction with nuclear and membrane-bound receptors, they regulate diverse physiological functions including lipid digestion/absorption, glucose homeostasis, energy expenditure, inflammatory responses, and cell survival. Dysregulation of these pathways contributes significantly to metabolic diseases such as type 2 diabetes mellitus, non-alcoholic fatty liver disease/NASH, cardiovascular disorders, and chronic inflammation. Therapeutic strategies have focused on modulating this axis using synthetic ligands for FXR/TGR5 or altering endogenous bile acids through sequestrants or analogs. However, "bile acid signaling" itself is not an individual therapeutic target but rather describes an integrated regulatory system involving multiple molecular targets within its pathway.[1][2][3][4][5]

Other names

Bile acid pathwayBile acid-mediated signaling

Drugs targeting bile acid signaling typically act by: – Agonizing or antagonizing nuclear receptors like FXR to regulate gene expression involved in lipid/glucose metabolism and inflammation. – Activating TGR5 to stimulate cAMP-dependent pathways affecting energy expenditure and anti-inflammatory effects[1][3].