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. The analysis using chimeric receptors revealed that ligand binding domain of PPARalpha and VDR was involved in the molecular basis of this functional interaction and that the DNA binding domain of VDR was not required for the suppression, suggesting a novel mechanism that might involve protein-protein interactions rather than a direct DNA binding. Furthermore, the treatment of rat hepatoma H4IIE cells with 1,25(OH)(2)D(3) diminishes the induction of AOX mRNA by PPARalpha ligands, Wy14,643. VDR signaling might be considered as a factor regulating lipid metabolism via PPARalpha pathway. We report here the novel action of VDR in controlling gene expression through PPARalpha signaling.
Sakuma
Takahiro
T
Department of Aging Medicine and Geriatrics, Shinshu University School of Medicine, 390-8621, Matsumoto, Japan
Miyamoto
Takahide
T
Jiang
Wei
W
Kakizawa
Tomoko
T
Nishio
Shin-ich
SI
Suzuki
Satoru
S
Takeda
Teiji
T
Oiwa
Ako
A
Hashizume
Kiyoshi
K
D000818:Animals; D019556:COS Cells; D002117:Calcitriol / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000502:physiology*; D018167:Receptors, Calcitriol / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism*
D018167:Receptors, Calcitriol; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D002117:Calcitriol