NR1H4 and obesity due to melanocortin 4 receptor deficiency: However, the FXR seems to have a tissue-specific action: (1) the intestinal FXR antagonism inhibits sterol regulatory element-binding protein-1 (SREBP-1) with positive effects on lipid metabolism; (2) conversely, its hepatic agonism increases insulin-sensitivity, reduces obesity and suppresses inflammation [11,65].