التفاصيل البيبلوغرافية
| العنوان: |
A newly identified CG301269 improves lipid and glucose metabolism without body weight gain through activation of peroxisome proliferator-activated receptor alpha and gamma. |
| المؤلفون: |
Jeong HW, Lee JW, Kim WS, Choe SS, Kim KH, Park HS, Shin HJ, Lee GY, Shin D, Lee H, Lee JH, Choi EB, Lee HK, Chung H, Park SB, Park KS, Kim HS, Ro S, Kim JB, Jeong, Hyun Woo |
| المصدر: |
Diabetes; Feb2011, Vol. 60 Issue 2, p496-506, 11p |
| مستخلص: |
Objective: Peroxisome proliferator-activated receptor (PPAR)-α/γ dual agonists have been developed to alleviate metabolic disorders. However, several PPARα/γ dual agonists are accompanied with unwanted side effects, including body weight gain, edema, and tissue failure. This study investigated the effects of a novel PPARα/γ dual agonist, CG301269, on metabolic disorders both in vitro and in vivo.Research Design and Methods: Function of CG301269 as a PPARα/γ dual agonist was assessed in vitro by luciferase reporter assay, mammalian one-hybrid assay, and analyses of PPAR target genes. In vitro profiles on fatty acid oxidation and inflammatory responses were acquired by fatty acid oxidation assay and quantitative (q)RT-PCR of proinflammatory genes. In vivo effect of CG301269 was examined in db/db mice. Total body weight and various tissue weights were measured, and hepatic lipid profiles were analyzed. Systemic glucose and insulin tolerance were measured, and the in vivo effect of CG301269 on metabolic genes and proinflammatory genes was examined by qRT-PCR.Results: CG301269 selectively stimulated the transcriptional activities of PPARα and PPARγ. CG301269 enhanced fatty acid oxidation in vitro and ameliorated insulin resistance and hyperlipidemia in vivo. In db/db mice, CG301269 reduced inflammatory responses and fatty liver, without body weight gain.Conclusions: We demonstrate that CG301269 exhibits beneficial effects on glucose and lipid metabolism by simultaneous activation of both PPARα and PPARγ. Our data suggest that CG301269 would be a potential lead compound against obesity and related metabolic disorders. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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