Inhibition of peroxisome proliferator-activated receptor α signaling by vitamin D receptor

Crosstalk between the peroxisome proliferator-activated receptor γ (PPARγ) and the vitamin D receptor (VDR) in human breast cancer cells: PPARγ binds to VDR and inhibits 1α,25-dihydroxyvitamin D3 mediated transactivation

“…Importantly, PPARg's DNA binding domain was not necessary for PPARg's suppressive effect on 1,25D 3 mediated action. Similar to our findings, Sakuma et al, [20] demonstrated that VDR in the presence of 1,25D 3 inhibits the transactivation of PPARa, another member of the PPAR family independent of the DNA binding domain.…”

“…Dunlop et al, [26] also showed that cross-talk between VDR and PPARd is modulated by the association of VDR at the proximal regions of PPARd 0 s promoter, containing VDRE. Furthermore, Sakuma et al, [20] implicated that protein-protein interactions between VDR and PPARa result in VDR's inhibitory effect on PPARa 0 s transcriptional activity. Thus, these observations indicate that proteinprotein or DNA-protein interactions link reciprocal nuclear receptor pathways.…”

1,25-dihydroxyvitamin D3 and its receptor inhibit the chenodeoxycholic acid-dependent transactivation by farnesoid X receptor

“…Intriguingly, this inhibitory effect on PPAR requires only VDR-LBD, and not the DBD. D3-bound VDR may target a common cofactor for LBD of FXR and PPAR (Sakuma et al 2003). Our GST pull-down assay indicated that FXR-LBD interacts with VDR, but not RAR , PPAR 2 and LXR (Fig.…”

“…This may also exclude the possibility that, via the classical VDRE, D3-bound VDR may induce some factor that can suppress the transactivation by CDCA/FXR. Sakuma et al (2003) reported that the transactivation by PPAR and its ligand, clofibric acid, is inhibited by D3-bound VDR, and not by estrogen/ estrogen receptor or dexamethasone/glucocorticoid receptor. Intriguingly, this inhibitory effect on PPAR requires only VDR-LBD, and not the DBD.…”

Vitamin D and Obesity

“…This cell line offers an ideal model system to understand adipocyte development. In rat hepatoma (H4IIE) cell lines, nuclear VDR represses the transcriptional activity of PPARα (but not PPARɤ) in a 1,25OHD 3 -dependent manner [127]. PPARα potentiates fatty acid catabolism in the liver and is activated by the lipid-lowering fibrates, whereas PPARɤ is essential for adipocyte differentiation.…”