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PPAR Research  2013 

Expression and Function of PPARs in Placenta

DOI: 10.1155/2013/256508

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Abstract:

Peroxisome proliferator-activated receptors (PPAR) are members of the superfamily of nuclear hormone receptors involved in embryonic development and differentiation of several tissues including placenta, which respond to specific ligands such as polyunsaturated fatty acids by altering gene expression. Three subtypes of this receptor have been discovered, each evolving to achieve different biological functions. The PPARs also control a variety of target genes involved in lipid homeostasis. Similar to other nuclear receptors, the transcriptional activity of PPARs is affected not only by ligand-stimulation but also by crosstalk with other molecules. For example, both PPARs and the RXRs are ligand-activated transcription factors that coordinately regulate gene expression. In addition, several mechanisms underlying negative regulation of gene expression by PPARs have been shown. It is suggested that PPARs are key messengers responsible for the translation of nutritional stimuli into changes in gene expression pathways for placental development. 1. Introduction Peroxisome proliferator-activated receptors (PPARs) are a family of ligand activated transcription factors belonging to the nuclear hormone receptor superfamily, which mainly regulate the expression of target genes involved in lipid and energy metabolism [1–3]. Three PPAR isotypes have been identified in mammals termed PPARα, PPARβ/δ, and PPARγ [4, 5]. Each isotype is a product of a separate gene, and each one has a distinct tissue distribution relating to the distinct functions. The PPARs play key roles in the metabolic syndrome and overall health of organisms including regeneration of tissues, differentiation, lipid metabolism, and immune response [6]. From a nutritional viewpoint, the PPARs are of importance because of their ability to be activated by long chain fatty acids and their metabolites [7]. Therefore, the PPARs are recognized as candidates in order to improve metabolism and health through suitable diet. In addition, several evidences show the important role of PPARs in reproductive organs [8, 9]. PPARγ expression has been found in the granulosa, theca, and luteal cells [10]. The PPARγ may regulate the differentiation and proliferation of the ovarian cells, steroidogenesis, angiogenesis, and prostaglandin production [11], indicating that PPARs modulate the estrous cycle and pregnancy. Retinoic X receptor (RXR) is a functional partner of PPAR. RXRα and PPARγ function potently in metabolic diseases and are both important targets for antidiabetic drugs. Coactivation of RXRα and PPARγ is

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