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PPARγ is a ligand-activated transcription factor involved in the regulation of lipid homeostasis and may function as a master regulator of adipogenesis.1,2,3,4 Ligands for PPARγ include antidiabetic drugs of the thiazolidinedione structural class, 15-deoxy-Δ12,14-prostaglandin J2, and NSAIDS.5,6,7,8 BADGE is a synthetic compound used in the production of polycarbonate and industrial plastics. This compound was recently identified as an antagonist of PPARγ.9 BADGE binds to PPARγ with an apparent Kd of 100 µM and interferes with the ability of 3T3-L1 and 3T3-F442A cells to undergo hormone-mediated cell differentiation.9
1
Elbrecht, A., Chen, Y., Cullinan, C.A., et al. Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors γ 1 and γ 2. Biochem Biophys Res Commun224431-437(1996).
2
Greene, M.E., Blumberg, B., McBride, O.W., et al. Isolation of the human peroxisome proliferator activated receptor γ cDNA: Expression in hematopoietic cells and chromosomal mapping. Gene Expr4281-299(1995).
3
Spiegelman, B.M., and Flier, J.S. Adipogenesis and obesity: Rounding out the big picture. Cell87377-389(1995).
4
Lemberger, T., Desvergne, B., and Wahli, W. Peroxisome proliferator-activated receptors: A nuclear receptor signaling pathway in lipid physiology. Annu Rev Cell Dev Biol12335-363(1996).
5
Lehmann, J.M., Moore, L.B., Smith-Oliver, T.A., et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ). J Biol Chem27012953-12956(1995).
6
Willson, T.M., Cobb, J.E., Cowan, D.J., et al. The structure-activity relationship between peroxisome proliferator-activated receptor γ agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem39665-668(1996).
7
Forman, B.M., Tontonoz, P., Chen, J., et al. 15-Deoxy-Δ12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ. Cell83803-812(1995).
8
Lehmann, J.M., Lenhard, J.M., Oliver, B.B., et al. Peroxisome proliferator-activated receptors a and g are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem2723406-3410(1997).
9
Wright, H.M., Clish, C.B., Mikami, T., et al. A synthetic antagonist for the peroxisome proliferator-activated receptor γ inhibits adipocyte differentiation. J Biol Chem2751873-1877(2000).
Forman, B.M., Tontonoz, P., Chen, J., et al. 15-Deoxy-Δ12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ. Cell83803-812(1995).
Greene, M.E., Blumberg, B., McBride, O.W., et al. Isolation of the human peroxisome proliferator activated receptor γ cDNA: Expression in hematopoietic cells and chromosomal mapping. Gene Expr4281-299(1995).
Lehmann, J.M., Lenhard, J.M., Oliver, B.B., et al. Peroxisome proliferator-activated receptors a and g are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem2723406-3410(1997).
Lemberger, T., Desvergne, B., and Wahli, W. Peroxisome proliferator-activated receptors: A nuclear receptor signaling pathway in lipid physiology. Annu Rev Cell Dev Biol12335-363(1996).
Elbrecht, A., Chen, Y., Cullinan, C.A., et al. Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors γ 1 and γ 2. Biochem Biophys Res Commun224431-437(1996).
Spiegelman, B.M., and Flier, J.S. Adipogenesis and obesity: Rounding out the big picture. Cell87377-389(1995).
Willson, T.M., Cobb, J.E., Cowan, D.J., et al. The structure-activity relationship between peroxisome proliferator-activated receptor γ agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem39665-668(1996).
Wright, H.M., Clish, C.B., Mikami, T., et al. A synthetic antagonist for the peroxisome proliferator-activated receptor γ inhibits adipocyte differentiation. J Biol Chem2751873-1877(2000).
Lehmann, J.M., Moore, L.B., Smith-Oliver, T.A., et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ). J Biol Chem27012953-12956(1995).