Identification of putative metabolites of docosahexaenoic acid as potent PPARgamma agonists and antidiabetic agents |
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| Authors: | Yamamoto Keiko Itoh Toshimasa Abe Daijiro Shimizu Masato Kanda Tomoatsu Koyama Takatoshi Nishikawa Masazumi Tamai Tadakazu Ooizumi Hiroshi Yamada Sachiko |
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| Affiliation: | Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. yamamoto.mr@tmd.ac.jp |
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| Abstract: | We found that putative metabolites of docosahexaenoic acid (DHA) are strong PPARgamma activators and potential antidiabetic agents. We designed DHA derivatives based on the crystal structure of PPARgamma, synthesized them and evaluated their activities in vitro and in vivo. The efficacy of 5E-4-hydroxy-DHA 2a as a PPARgamma activator was about fourfold stronger than that of pioglitazone. Furthermore, the 4-keto derivative (10b) showed antidiabetic activity in animal models without producing undesirable effects such as obesity and hepatotoxicity. |
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