**12.5 Bile acid agonists (INT-777, INT-747): supporting liver function and gut epithelial signaling**

Bile acids play a crucial role in maintaining lipid and glucose metabolism via G-protein coupled receptor (TGR5) and farnesoid X receptor (FXR) signaling. FXR regulates key pathways involved in metabolism in the liver. Alteration in bile acid signaling reduces bile acid synthesis in the liver and leads to hepatic cholestasis and inflammation [160, 161]. Recent literature suggests that altered bile acid signaling increases insulin resistance and promotes hepatic gluconeogenesis [162, 163]. TGR5 activates the cAMP/PKA pathway to regulate lipid metabolism. INT-777 and INT-747, novel and selective agonists of TGR5 and FXR respectively, stimulate bile flow. INT-777/TGR5 activation inhibits nuclear translocation of NFkB and displays an anti-inflammatory effect by reducing the secretion of TNF-α, IL-6, IL-1β and IFN-γ. Bile acids activate FXR, which regulates the transcription of FGF19 and binds to FGFR4. FGFR4 blocks CYP7A1 and represses bile acid synthesis [164, 165].

*Parenteral Nutrition Modeling and Research Advances DOI: http://dx.doi.org/10.5772/intechopen.101692*

Treatment using bile acid receptor agonists INT-777 (TGR5) and obeticholic acid/ INT-747 (FXR) can attenuate hepatic steatosis and improve the overall metabolic profile induced by high fat diet (HFD). Animal models show that INT-747 and INT-777 supplementation promote fatty acid oxidation in the liver by regulating the expression of key genes (*acyl-CoA oxidase* and *carnitine palmitoyltransferase*) involved in fatty acid metabolism [166, 167].
