Physiological and pharmacological function of PPARs.

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  • TAKAHASHI Nubuyuki
    Research Project for Obesity and Lipid Metabolism Regulation, Bio-oriented Research Advancement Institution (BRAIN)
  • KAWADA Teruo
    Department of Applied Life Sciences, Kyoto University

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  • ＰＰＡＲｓの生理・薬理機能
  • PPARs ノ セイリ ヤクリ キノウ

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The finding of nuclear receptors has greatly enhanced our understanding of gene regulation by lipophilic hormones such as steroids, thyroxine, vitamin D and retinoids. These receptors comprise a superfamily of transcription factors containing highly related DNA-binding domains. In mammals, the peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone receptors consists of three subtypes by separate genes: PPARα, PPARδ (also referred to as hNUC1 or PPARβ), and PPARγ. PPARs have been associated with several distinct biological programs. PPARs function as a heterodimer with the retinoid X receptor. This complex binds to sequences termed direct repeat-1 response element in enhancer sites of regulated genes and activates transcription upon ligand and coactivator binding. Three different PPAR subtypes have specific roles in different organs. PPARα, mainly expressed in liver, plays an important role in fatty acid metabolism. PPARγ predominantly is expressed in adipose cells. PPARδ displays a high level of expression in lipid-metabolizing organs such as small intestine, heart and adipose tissue. Naturally occurring and synthetic molecules (anti-hyperlipidemia and diabetic drugs) that are ligands for these nuclear receptors control transcriptional activity of PPARs. We believe that the pharmacological and genomic researches on PPAR will develop powerful tools for prevention and medical care against common diseases.

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