Abstract
We have examined the modulating action of xanthohumol (XN) on the farnesoid X receptor (FXR) in vitro and in vivo. In the transient transfection assay, XN dose-dependently increased the BSEP promoter-driven luciferase activity. XN-fed KK- A y mice exhibited lowered levels of plasma glucose, plasma, and hepatic triglyceride. They also showed decreased amounts of water intake, lowered weights of white adipose tissue, and exhibited increased levels of plasma adiponectin, indicating that XN attenuated diabetes in KK- A y mice. The hepatic gene expression of XN-fed mice showed lowered levels of SREBP-1c including its targets involved in fatty acid synthesis and lowered levels of gluconeogenetic genes. However, the expression of cholesterol 7-hydroxylase (CYP7A1) was significantly induced in the liver of XN-fed mice. From the present results, it is suggested that XN acts on FXR through a selective bile acid receptor modulator (SBARM) like guggulsterone or polyunsaturated fatty acids, which have previously been reported as SBARMs.
Published Version
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