NR1H4 and obesity due to melanocortin 4 receptor deficiency: Studies in FXR-deficient mice fed a HFD have demonstrated that intestinal flora takes part in the development of IR and obesity by modulating BA and FXR signaling, and conversely, FXR may contribute to adiposity increase by changing the composition of gut microbiome, which is characterized by elevation in Bacteroidetes and reduction in Firmicutes (153).