Inhibition of LXRalpha signaling by vitamin D receptor: possible role of VDR in bile acid synthesis.

The expression of cholesterol 7alpha-hydroxylase (CYP7alpha), the rate-limiting enzyme in the catabolism of cholesterol to bile acid, is stimulated by oxysterol receptor, liver X receptor alpha (LXRalpha) and negatively regulated by a bile acid receptor, farnesoid X receptor. In the current study, we demonstrated that 1,25-(OH)(2)D3 blunted the LXRalpha-mediated induction of CYP7alpha mRNA in H4IIE rat hepatoma cells. In co-transfection experiments in HepG2 cells, VDR repressed the activity of rat CYP7alpha promoter in a ligand-dependent manner through inhibition of LXRalpha signaling.

Inhibition of peroxisome proliferator-activated receptor alpha signaling by vitamin D receptor.

Peroxisome proliferator-activated receptors (PPARs) are nuclear fatty acid receptors that have been implicated to play an important role in lipid and glucose homeostasis. PPARalpha potentiates fatty acid catabolism in the liver and is activated by the lipid-lowering fibrates, whereas PPARgamma is essential for adipocyte differentiation. Here we report that nuclear vitamin D(3) receptor (VDR) represses the transcriptional activity of PPARalpha but not PPARgamma in a 1,25(OH)(2)D(3)-dependent manner.