NR1H4 and obesity due to melanocortin 4 receptor deficiency: BAs play multiple roles in the control of obesity/T2D related glucose and lipid metabolism, and energy homeostasis by activating the nuclear FXR and the cytoplasmic G protein-coupled membrane receptor 5 (TGR5) which regulate a large number metabolic pathways in the host (Thomas et al., 2008, 2009; Wahlstrom et al., 2016).