As a whole, PXR and CAR appear to cooperate with FXRα for protection against endobiotic and xenobiotic toxicity, making these NRs interesting targets for therapeutical approaches in the treatment of metabolic disorders, although their role beyond being BA/xenobiotic NRs need to be expanded to include their effects on health and diseases, while minimizing adverse diet-drug or drug-drug interactions (DDIs) in patients with chronic diseases. This evidence concerns the gene NR1I3 and metabolic disease.