Enhancement of the Aquaporin Adipose Gene Expression by a Peroxisome Proliferator-activated Receptor γ
Autor: | Tohru Funahashi, Hiroyuki Nagaretani, Hidehiko Kondo, Ken Kishida, Yuji Matsuzawa, Norikazu Maeda, Kikuko Hotta, Hiroshi Kuriyama, Hitoshi Nishizawa, Noriyuki Ouchi, Shinji Kihara, Iichiro Shimomura, Morihiro Matsuda, Takashi Kadowaki |
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Rok vydání: | 2001 |
Předmět: |
Male
Receptor complex Response element Receptors Cytoplasmic and Nuclear Adipose tissue Peroxisome proliferator-activated receptor Biology Aquaporins Biochemistry Mice Gene expression Animals Electrophoretic mobility shift assay RNA Messenger Promoter Regions Genetic Receptor Molecular Biology DNA Primers chemistry.chemical_classification Regulation of gene expression Base Sequence 3T3 Cells Cell Biology Molecular biology Mice Inbred C57BL Thiazoles Adipose Tissue Gene Expression Regulation chemistry Thiazolidinediones Transcription Factors |
Zdroj: | Europe PubMed Central |
ISSN: | 0021-9258 |
DOI: | 10.1074/jbc.m108213200 |
Popis: | 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. |
Databáze: | OpenAIRE |
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