The study identifies mPPARγ2 as a key regulator of adipocyte-specific gene expression. Researchers isolated and characterized an enhancer from the adipocyte P2 (aP2) gene that directs high-level adipocyte-specific gene expression in cultured cells and transgenic mice. The key regulator of this enhancer is ARF6, a cell type-restricted nuclear factor. The study shows that mPPARγ2, a novel member of the peroxisome proliferator-activated receptor (PPAR) family, forms a heterodimer with RXRα and constitutes a functional ARF6 complex. mPPARγ2 is highly specific for adipose tissue and is sufficient to activate the adipocyte-specific aP2 enhancer in heterologous cell types. The study demonstrates that mPPARγ2 and RXRα activate the aP2 enhancer in cultured fibroblasts, and this activation is potentiated by peroxisome proliferators, fatty acids, and 9-cis retinoic acid. These results identify mPPARγ2 as the first adipocyte-specific transcription factor and suggest mechanisms by which fatty acids, peroxisome proliferators, 9-cis retinoic acid, and other lipids may regulate adipocyte gene expression and differentiation. The study also shows that mPPARγ2 binds to ARF6-binding sites in the aP2 enhancer and that the mPPARγ2/RXRα heterodimer has DNA-binding and transcriptional activation properties identical to those of the adipocyte transcription factor ARF6. The study concludes that mPPARγ2 is the functional ARF6 complex in vivo and plays a central role in adipocyte gene expression and differentiation.The study identifies mPPARγ2 as a key regulator of adipocyte-specific gene expression. Researchers isolated and characterized an enhancer from the adipocyte P2 (aP2) gene that directs high-level adipocyte-specific gene expression in cultured cells and transgenic mice. The key regulator of this enhancer is ARF6, a cell type-restricted nuclear factor. The study shows that mPPARγ2, a novel member of the peroxisome proliferator-activated receptor (PPAR) family, forms a heterodimer with RXRα and constitutes a functional ARF6 complex. mPPARγ2 is highly specific for adipose tissue and is sufficient to activate the adipocyte-specific aP2 enhancer in heterologous cell types. The study demonstrates that mPPARγ2 and RXRα activate the aP2 enhancer in cultured fibroblasts, and this activation is potentiated by peroxisome proliferators, fatty acids, and 9-cis retinoic acid. These results identify mPPARγ2 as the first adipocyte-specific transcription factor and suggest mechanisms by which fatty acids, peroxisome proliferators, 9-cis retinoic acid, and other lipids may regulate adipocyte gene expression and differentiation. The study also shows that mPPARγ2 binds to ARF6-binding sites in the aP2 enhancer and that the mPPARγ2/RXRα heterodimer has DNA-binding and transcriptional activation properties identical to those of the adipocyte transcription factor ARF6. The study concludes that mPPARγ2 is the functional ARF6 complex in vivo and plays a central role in adipocyte gene expression and differentiation.