Peroxisome proliferator-activated receptor

In the field of molecular biology, the peroxisome proliferator–activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating gene expression. PPARs play essential roles in regulating cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis

Three types of PPARs have been identified: alpha, gamma, and delta (beta):

These agents, pharmacologically related to the fibrates, were discovered in the early 1980s.

PPARs were originally identified in Xenopus frogs as receptors that induce the proliferation of peroxisomes in cells in 1992. The first PPAR (PPARα) was discovered in 1990 during the search for a molecular target of a group of agents then referred to as peroxisome proliferators, as they increased peroxisomal numbers in rodent liver tissue, apart from improving insulin sensitivity.

When it turned out that PPARs played a versatile role in biology, the agents were in turn termed PPAR ligands. The best-known PPAR ligands are the thiazolidinediones.

After PPARδ (delta) was identified in humans in 1992, it turned out to be closely related to PPARβ (beta), previously described during the same year in an amphibian, Xenopus. The term "PPARδ" is generally used in the US, while "PPARβ" has remained in Europe, where this receptor was initially discovered.

PPARs were named because they induce peroxisome proliferation in rodents, but this induction has not been verified in humans.

All PPARs heterodimerize with the retinoid X receptor (RXR) and bind to specific regions on the DNA of target genes. These DNA sequences are termed PPREs (peroxisome proliferator hormone response elements). The DNA consensus sequence is AGGTCANAGGTCA, with N being any nucleotide. In general, this sequence occurs in the promoter region of a gene, and, when the PPAR binds its ligand, transcription of target genes is increased or decreased, depending on the gene. The RXR also forms a heterodimer with a number of other receptors (e.g., vitamin D and thyroid hormone).