Enhancement of the aquaporin adipose gene expression by a peroxisome proliferator-activated receptor gamma.
The current study demonstrates that aquaporin adipose (AQPap), an adipose-specific glycerol channel (Kishida, K., Kuriyama, H., Funahashi, T., Shimomura, I., Kihara, S., Ouchi, N., Nishida, M., Nishizawa, H., Matsuda, M., Takahashi, M., Hotta, K., Nakamura, T., Yamashita, S., Tochino, Y., and Matsuzawa, Y. (2000) J. Biol. Chem. 275, 20896-20902), is a target gene of peroxisome proliferator-activated receptor (PPAR) gamma. The AQPap mRNA amounts increased following the induction of PPARgamma in the differentiation of 3T3-L1 adipocytes. The AQPap mRNA in the adipose tissue increased when mice were treated with pioglitazone (PGZ), a synthetic PPARgamma ligand, and decreased in PPARgamma(+/-) heterozygous knockout mice. In 3T3-L1 adipocytes, PGZ augmented the AQPap mRNA expression and its promoter activity. Serial deletion of the promoter revealed the putative peroxisome proliferator-activated receptor response element (PPRE) at -93/-77. In 3T3-L1 preadipocytes, the expression of PPARgamma by transfection and PGZ activated the luciferase activity of the promoter containing the PPRE, whereas the PPRE-deleted mutant was not affected. The gel mobility shift assay showed the direct binding of PPARgamma-retinoid X receptor alpha complex to the PPRE. DeltaPPARgamma, which we generated as the dominant negative PPARgamma lacking the activation function-2 domain, suppressed the promoter activity in 3T3-L1 cells, dose-dependently. We conclude that AQPap is a novel adipose-specific target gene of PPARgamma through the binding of PPARgamma-retinoid X receptor complex to the PPRE region in its promoter.
Kishida
K
K
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita 565-0871, Japan.
Shimomura
I
I
Nishizawa
H
H
Maeda
N
N
Kuriyama
H
H
Kondo
H
H
Matsuda
M
M
Nagaretani
H
H
Ouchi
N
N
Hotta
K
K
Kihara
S
S
Kadowaki
T
T
Funahashi
T
T
Matsuzawa
Y
Y
D016475:3T3 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D020346:Aquaporins / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000502:physiology*
D020346:Aquaporins; D017931:DNA Primers; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C089946:2,4-thiazolidinedione