A transcription factor in the adipogenic (fat synthetic) pathways. The three types α, γ, and δ show different distribution in human tissues and associate with different ligands. PPARα is the target for the drugs and fibrates (amphipatic carboxylic acids) that reduce triglycerides. Type α also acts as a transcription factor for several genes affecting lipoprotein and fatty acid metabolism. PPARγ is a (3p25) regulator of glucose, lipid, and cholesterol metabolism, may be sensitized by thiazolidinediones (TZD), and offers some hope to be used for the treatment of diabetes mellitus type2 (IDDM). PPARγ2 deficiency dramatically reduces adipogenesis in mouse fibroblasts whereas PPARγ1 affects obesity and diabetes (Zhang J et al 2004 Proc Natl Acad Sci USA 101:10703). The PPARγ 12Ala allele is associated with a small yet significant reduction in the risk for diabetes type II. PPARγ agonists have a controversial—promoting and suppressing—effect on polyposis of the colon and other cancers. In human thyroid carcinoma, PAX8–PPARγ1 has been observed. PPAR-α agonists are also successful for the treatment of some autoimmune diseases. PPARγ deficiency can also lead to hypertension. peroxisome, ROS, diabetes mellitus, polyposis, farnesoid X receptor, leukotrienes, leptin, obesity, Krox20, hypertension, pax, thiazolidinedione, dizygotic twins, sirtuin, mesenchyma, retinoic acid; Lowell BB 1999 Cell 99:239; Kersten S et al 2000 Nature 405:421; Willson TM et al 2001 Annu Rev Biochem 70:341; Michalik L et al 2004 Nature Rev Cancer 4:61; review: Lehrke M, Lazar MA 2005 Cell 123:993.
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