Notably, pharmacological agonism of FXR with obeticholic acid (OCA) in preclinical studies in rodents led to a significant decrease of low-density lipoprotein (LDL) cholesterol9, 10, whereas OCA administration to healthy volunteers11 and to non-alcoholic fatty liver disease (NAFLD) patients in clinical trials12 had the opposite effect: it led to a substantial increase of LDL cholesterol in the blood. This evidence concerns the gene NR1H4 and metabolic dysfunction-associated steatotic liver disease.