Enhancement of the Aquaporin Adipose Gene Expression by a Peroxisome Proliferator-activated Receptor γ*

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) γ. The AQPap mRNA amounts increased following the induction of PPARγ in the differentiation of 3T3-L1 adipocytes. The AQPap mRNA in the adipose tissue increased when mice were treated with pioglitazone (PGZ), a synthetic PPARγ ligand, and decreased in PPARγ+/− 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 PPARγ 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 PPARγ-retinoid X receptor α complex to the PPRE. ΔPPARγ, which we generated as the dominant negative PPARγ 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 PPARγ through the binding of PPARγ-retinoid X receptor complex to the PPRE region in its promoter.

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