Cover story

Bile acids have been traditionally viewed as detergent molecules involved in the solubilization and absorption of lipids and lipidsoluble vitamins from the intestines. However, as a result of intensive research over the past two decades, bile acids are now viewed as endocrine signaling molecules that activate specific nuclear receptors and G-protein coupled receptors regulating nutrient metabolism in the liver and intestines. The year 2015 marks the 20-year anniversary of the cloning and discovery of farnesoid X receptor (NR4H1; FXR). FXR is a main bile acid nuclear receptor and plays an essential role in the regulation of bile acids, lipids, glucose and drug metabolism, as well as inhibiting inflammation and suppressing carcinogenesis in the liver and intestine. Bile acids also activate pregnane X receptor, constitutive androstane receptor, vitamin D receptor, G protein–coupled bile acid receptor (TGR5), and sphingosine-1-phosphate receptor 2 (S1PR2) to regulate growth and functions of hepatocytes, cholangiocytes and enterocytes. Moreover, bile acids also induce, via FXR, critical regulators of metabolism, inflammation and carcinogenesis in the liver and intestine, including small heterodimer partner (SHP) and fibroblast growth factor 15/19 (FGF15/19). The