NR1H4 and fatty liver disease: Abnormal BA metabolism promotes hepatitis and fibrosis.186,187 BAs can regulate lipid synthesis by stimulating FXR; in addition, BAs and the gut microbiota can regulate each other and subsequently promote the development of NAFLD and NASH.188 Many FXR and TGR5 activators have been detected in BA analogs to reduce hepatic steatosis and inflammation, such as obeticholic acid, which has been recognized as a new treatment for NASH and cholestatic diseases.189,190 Suppressed hepatic bile acid signaling despite elevated production of primary and secondary BAs in NAFLD.191