In addition, improved glucose homeostasis and insulin resistance have been reported in FXR-deficient, but not in liver-specific FXR deficient, obese mice as well as after application of the FXR antagonist HS218 in a mouse model of type 2 diabetes (Prawitt et al., 2011; Xu et al., 2018). Here, NR1H4 is linked to type 2 diabetes mellitus.