Preclinical studies: INT-777 (TGR5 agonist) improved insulin sensitivity and reduced hepatic steatosis in obese mice. A novel agonist (RDX8940) increased GLP-1/PYY and decreased liver fat in diet-induced NAFLD mice. INT-767 (dual FXR/TGR5 agonist) reduced liver fibrosis and inflammation in NASH models. Clinical data: No TGR5-specific agonist has been approved yet; development has been limited by TGR5-mediated gallbladder effects. Here, NR1H4 is linked to fatty liver disease.