PPARG / PPAR Gamma

peroxisome proliferator-activated receptor gamma

Peroxisome proliferator-activated receptor gamma (PPAR gamma), a NR1 Thyroid Hormone-Like Receptor, is a transcription factor that regulates genes involved in lipid metabolism and adipocyte differentiation and has been shown to affect placental differentiation and cell proliferation and differentiation pathways in various diseases such as Type II diabetes and atherosclerosis. Recently, PPAR gamma has been suggested to affect inflammatory digestive diseases (Dubuquoy et al. 2002). PPAR gamma binds target DNA as a heterodimer (with retinoid X receptors) and has several coactivators, including steroid receptor coactivator-1 (SRC-1) and PPAR-binding protein (PBP). Two isoforms of PPAR gamma protein have been identified: PPAR gamma2 contains 30 additional amino acids at the N terminus compared to PPAR gamma1. PPAR gamma2 is expressed mainly in adipose tissue, whereas PPAR gamma1 is expressed widely. Mutations in PPAR gamma2 have been implicated in the development of obesity and Type II diabetes. PPAR gamma is the molecular target of thiazolidinediones (TZDs), drugs used widely for treatment of Type II diabetes, and is believed to mediate the apoptotic effects of this class of drugs in a variety of cell types, including B and T lymphocytes. Altered expression of PPAR gamma and cyclooxygenase-2 (COX-2) and the subsequent modulation in the tissue levels of PGE(2) and 15-d-PGJ(2) may influence the development of human breast cancer and its progression to metastasis.

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