Retinoic acid amplifies the FXR-dependent FGF19 gene expression in human enterocyte-like HT-29 cells by a bi-phasic mechanism

Background and aims: The intestine-derived hormone Fibroblast Growth Factor 19 (FGF19) and its mouse ortholog Ffg15 are key regulators of bile acid synthesis and energy metabolism. FGF15/19 expression is induced by bile acid-mediated activation of FXR. Moreover, vitamin A (VA) has been shown to activate Fgf15 in an RXR/FXR-dependent manner in mice. Whether VA derivatives regulate FGF19 in human enterocytes and which nuclear receptors contribute to this regulation is currently unknown. Methods: HT-29 cells were treated with VA derivatives with distinct selectivity for different nuclear receptors including 9-cis r…