In this respect, the simultaneous deficiency of FXR and TGR5 dramatically worsens atherosclerosis development and aortic inflammation in Ldlr-/- mice fed a high-fat diet [226], whereas the administration of a potent dual activator for FXR and TGR5 significantly reduces atherosclerotic plaque formation [227]. The gene discussed is NR1H4; the disease is atherosclerosis.