In vivo studies proved that the inhibition of intestinal FXR signaling could reduce obesity, insulin resistance, and fatty liver disease by regulating enterohepatic BA metabolism and intestinal ceramide synthesis (Cariou et al., 2006; Prawitt et al., 2011; Gonzalez et al., 2016). Here, NR1H4 is linked to obesity due to melanocortin 4 receptor deficiency.