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http://ir.nhri.org.tw/handle/3990099045/17014
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| Title: | Identification of PTGR2 inhibitors as a new therapeutic strategy for diabetes and obesity |
| Authors: | Chang, YC;Hsieh, ML;Lee, HL;Hee, SW;Chang, CF;Yen, HY;Chen, YA;Chen, YR;Chou, YW;Li, FA;Ke, YY;Chen, SY;Hung, MS;Hung, AF;Huang, JY;Chiu, CH;Lin, SY;Shih, SF;Hsu, CN;Hwang, JJ;Yeh, TK;Cheng, TR;Liao, KC;Laio, D;Lin, SW;Chen, TY;Hu, CM;Vogel, U;Saar, D;Kragelund, BB;Tsou, LK;Tseng, YH;Chuang, LM |
| Contributors: | Institute of Biotechnology and Pharmaceutical Research |
| Abstract: | Peroxisome proliferator-activated receptor γ (PPARγ) is a master transcriptional regulator of systemic insulin sensitivity and energy balance. The anti-diabetic drug thiazolidinediones (TZDs) are potent synthetic PPARγ ligands with undesirable side effects, including obesity, fluid retention, and osteoporosis. 15-keto prostaglandin E2 (15-keto-PGE2) is an endogenous PPARγ ligand metabolized by prostaglandin reductase 2 (PTGR2). Here, we confirmed that 15-keto-PGE2 binds to and activates PPARγ via covalent binding. In patients with type 2 diabetes and obese mice, serum 15-keto-PGE2 levels were decreased. Administration of 15-keto-PGE2 improves glucose homeostasis and prevented diet-induced obesity in mice. Either genetic inhibition of PTGR2 or PTGR2 inhibitor BPRPT0245 protected mice from diet-induced obesity, insulin resistance, and hepatic steatosis without causing fluid retention and osteoporosis. In conclusion, inhibition of PTGR2 is a new therapeutic approach to treat diabetes and obesity through increasing endogenous PPARγ ligands while avoiding side effects including increased adiposity, fluid retention, and osteoporosis. |
| Date: | 2025-03-21 |
| Relation: | EMBO Molecular Medicine. 2025 Mar 21;Article in Press. |
| Link to: | http://dx.doi.org/10.1038/s44321-025-00216-4 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1757-4676&DestApp=IC2JCR |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=105000556051 |
| Appears in Collections: | [鄒倫] 期刊論文
[洪明秀] 期刊論文
[葉燈光] 期刊論文
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| PUB40119175.pdf | | 4593Kb | Adobe PDF | 6 | View/Open | | PUB40119175.pdf.pdf | | 4593Kb | Adobe PDF | 8 | View/Open |
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