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    Peroxisome Proliferator-Activated Receptors (PPARs)
    Experiments, Studies and Background Information
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    Studies and Experiments

    • PPAR expression and function during vertebrate development [View Experiment]
    • Peroxisome Proliferator-Activated Receptor Negatively Regulates T-bet Transcription Through Suppression of p38 Mitogen-Activated Protein Kinase Activation [View Experiment]
    • Cyclin D3 Promotes Adipogenesis through Activation of Peroxisome Proliferator-Activated Receptor Gama [View Experiment]
    • Activation of Peroxisome Proliferator-Activated Receptors (PPARs) by Their Ligands and Protein Kinase A Activators [View Experiment]
    • Suppression of Retinal Peroxisome Proliferator-Activated Receptor Gama in Experimental Diabetes and Oxygen-Induced Retinopathy: Role of NADPH Oxidase [View Experiment]
    • Ligand-induced Peroxisome Proliferator-activated Receptor a Conformational Change [View Experiment]
    • S 26948: a New Specific Peroxisome Proliferator–Activated Receptor Gama Modulator With Potent Antidiabetes and Antiatherogenic Effects [View Experiment]
    • Thesis: Regulation of Peroxisome Proliferator-Activated Receptor Alpha by Selected Beta-Apocarotenoids [View Experiment]
    • Dissertation: Defining the Metabolic Effect of Peroxisome Proliferator-Activated Receptor δ Activation [View Experiment]
    Peroxisome Proliferator-Activated Receptors (PPARs)

    Definition

    The peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes.

    Topics of Interest

    PPARs play essential roles in the regulation of cellular differentiation, development, and metabolism (carbohydrate, lipid, protein), and tumorigenesis of higher organisms.

    Three types of PPARs have been identified: alpha, gamma, and delta (beta) which are expressed in different human body organs.

    History: PPARs were originally identified in Xenopus frogs as receptors that induce the proliferation of peroxisomes in cells. The first PPAR (PPARα) was discovered during the search of a molecular target for a group of agents then referred to as peroxisome proliferators, as they increased peroxisomal numbers in rodent liver tissue, apart from improving insulin sensitivity. These agents, pharmacologically related to the fibrates were discovered in the early 1980s. When it turned out that PPARs played a much more versatile role in biology, the agents were in turn termed PPAR ligands. The best-known PPAR ligands are the thiazolidinediones; see below for more details.

    After PPARδ (delta) was identified in humans in 1992, it turned out to be closely-related to the PPARβ (beta) previously described during the same year in other animals (Xenopus). The name PPARδ is generally used in the US, whereas the use of the PPARβ denomination has remained in Europe where this receptor was initially discovered in Xenopus.

    All PPARs heterodimerize with the liver X receptor, which subsequently heterodimerised 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 AGGTCAXAGGTCA, with X being a random nucleotide. In general, this sequence occurs in the promotor 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).

    Hereditary disorders of all PPARs have been described, generally leading to a loss in function and concomitant lipodystrophy, insulin resistance, and/or acanthosis nigricans. Of PPARγ, a gain-of-function mutation has been described and studied (Pro12Ala) which decreased the risk of insulin resistance; it is quite prevalent (allele frequency 0.03 - 0.12 in some populations). In contrast, pro115gln is associated with obesity. Some other polymorphisms have high incidence in populations with elevated body mass indexes.

    Like other nuclear receptors, PPARs are modular in structure and contain a few functional domains.

    PPAR modulators are drugs which act upon the peroxisome proliferator-activated receptor.

    Source: Wikipedia (All text is available under the terms of the GNU Free Documentation License and Creative Commons Attribution-ShareAlike License.)

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