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The Peroxisome-Proliferator-Activated Receptors
a Istanbul University Cerrahpasa Medical Faculty, Department of Medicine, Division of Endocrinology and Metabolism, Istanbul 34303, Turkey
Key Words: stress • metabolic syndrome x • peroxisome-proliferator-activated receptors • glucocorticoids, 11  -hydroxysteroid dehydrogenase
Address for correspondence: Volkan D. Yumuk, M.D., F.A.C.P., F.A.C.E., Istanbul University Cerrahpasa Medical Faculty, Department of Medicine, Division of Endocrinology and Metabolism, 34303 Istanbul, Turkey. Voice: 90-542-315-2161; fax: 90-212-414-3540. e-mail: volkanyumuk{at}superonline.com
The three peroxisome-proliferator-activated receptor (PPAR) subtypes PPAR-
 , PPAR- , and PPAR- are ligand-activated transcription factors of the nuclear receptor family. PPARs form obligate heterodimers with the retinoid X receptor, which bind to peroxisome-proliferator-response elements (PPREs). PPAR- is expressed mainly in liver, brown fat, kidney, heart, and skeletal muscle; PPAR- in intestine and adipose tissue; PPAR- and PPAR- are both expressed in vascular endothelium, smooth muscle cells, macrophages, and foam cells; PPAR- in skeletal muscle, human embryonic kidney, intestine, heart, adipose tissue, developing brain, and keratinocytes. Intense interest in the development of drugs with new mechanisms of action for the metabolic syndrome has focused attention on nuclear receptors, such as PPARs that function as regulators of energy homeostasis. Agonists of PPAR- and PPAR- are currently used to treat diabetic dyslipidemia and type 2 diabetes. Dual PPAR-/ agonists and PPAR-// pan-agonists are under investigation for treatment of cardiovascular disease and the metabolic syndrome. Selective PPAR modulators (SPPARMs) are PPAR ligands that possess desirable efficacy and improved tolerance. Efforts are being made to identify novel partial agonists or antagonists for PPAR- in order to combine their antidiabetic and antiobesity effects. Glucocorticoids are major mediators of the stress response and could be the link between stress and PPAR activator signaling and thus may affect the downstream metabolic pathways involved in fuel homeostasis.
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