An update on the mechanisms of action of the peroxisome proliferator-activated receptors (PPARs) and their roles in inflammation and cancer.
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors and have been initially described as molecular targets for compounds which induce peroxisome proliferation. The interest of researchers for PPARs increased dramatically when these receptors were shown to be directly activated by a number of medically relevant compounds. These compounds include: the fibrate class of hypolidemic drugs, the thiazolidinediones, which are insulin sensitizers used as orally active antidiabetic agents, certain non-steroidal anti-inflammatory drugs (NSAIDs), and naturally occurring fatty acid-derived molecules. Rapidly, it was demonstrated that PPARs are key regulators of lipid homeostasis and provide a molecular link between nutrition and gene regulation. Recently, detailed studies of PPAR expression profiles in different tissues pointed to the roles these receptors play in inflammation control and cell proliferation. In this review we will focus on the new insights gained into these two areas and we will also discuss our current knowledge of the regulation of PPAR transcriptional activity by cofactors.
INSERM U 325, Département d'Athérosclérose, Institut Pasteur, Lille, France.
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Gelman
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Fruchart
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Auwerx
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003110:Colonic Neoplasms / Q000139:chemically induced; D004734:Energy Metabolism / Q000502:physiology; D005227:Fatty Acids / Q000009:adverse effects / Q000494:pharmacology; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology; D050356:Lipid Metabolism; D008264:Macrophages / Q000166:cytology; D009369:Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D020025:Peroxisome Proliferators / Q000009:adverse effects / Q000494:pharmacology*; D020033:Protein Isoforms / Q000187:drug effects / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology*; D011987:Receptors, Steroid / Q000502:physiology; D013844:Thiazoles / Q000009:adverse effects / Q000494:pharmacology; D014157:Transcription Factors / Q000187:drug effects / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D020025:Peroxisome Proliferators; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D013844:Thiazoles; D014157:Transcription Factors