NR1H4 and metabolic disease: Different from the promotional effects of ceramide toward metabolic disorders, activation of intestinal FXR with an intestine-restricted agonist, fexaramine, results in decreased HFD-induced metabolic phenotypes in mice by increasing FGF15 synthesis, which is delivered to the liver where it decreases the expression of the hepatic BA synthesis enzyme cytochrome P450 family 7 subfamily A member 1 (CYP7A1) [71].