NR1H4 and obesity due to melanocortin 4 receptor deficiency: Given that long-term activation of FXR is reported to induce obesity [17] and that activation of TGR5 alone has a limited effect on lipid metabolism, our data suggest that targeting both FXR and TGR5 is a more attractive strategy for treatment of common metabolic disorders, such as obesity, NAFLD, and atherosclerosis.