Figure 6.

Potential roles of bile acid signaling in NAFLD progression. Under homeostatic conditions in the liver, TGR5 and S1PR2 are two of the apical membrane bile acid (BA) receptors present on cholangiocytes and are predominantly responsible for bile acid signaling across the biliary epithelium. An increase in total bile acids is a feature observed in NAFLD patients and in murine models. This can be primarily a result of reduced expression and localization of TGR5 or S1PR2 on the apical membrane and reduced FXR activation in cholangiocytes, which usually binds to bile acids and facilitates downstream pathways. This event might be considered as the initiation of a cascade of signaling events that ultimately leads to disruption of bile homeostasis across the biliary epithelium, thereby contributing to the NAFLD phenotype. Image made with BioRender (https://biorender.com/).