Potent PPARα activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice.

Potent PPARα activator derived from tomato juice, 13-oxo-9,11-octadecadienoic acid, decreases plasma and hepatic triglyceride in obese diabetic mice.
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DOI:
10.1371/journal.pone.0031317
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Kawada T
Kawada T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kim YI;Hirai S;Goto T;Ohyane C;Takahashi H;Tsugane T;Konishi C;Fujii T;Inai S;Iijima Y;Aoki K;Shibata D;Takahashi N;Kawada T

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血脂异常是几种肥胖相关疾病发展的主要危险因素。过氧化物酶体增殖物激活受体α(peroxisome proliferator-activated receptor α,PPARα)是一种配体激活的转录因子,调节能量代谢。以前,我们报道了9-oxo-10,12-octadecadienoic acid(9-oxo-ODA)存在于新鲜番茄果实中,并作为PPARα激动剂。除了9-氧代-ODA之外,我们还开发了13-氧代-9,11-十八碳二烯酸(13-氧代-ODA),它是9-氧代-ODA的异构体,仅存在于番茄汁中。在这项研究中,我们探讨了13-oxo-ODA在体外作为PPARα激动剂的可能性,以及其在体内是否能改善血脂异常和肝脂肪变性。体外荧光素酶实验表明,13-oxo-ODA可显著诱导PPARα活化,其荧光素酶活性强于9-oxo-ODA和共轭亚油酸(CLA),共轭亚油酸是13-oxo-ODA的前体,是一种有效的PPARα活化剂。除了体外实验外,用13-氧代-ODA治疗还降低了喂食高脂饮食的肥胖KK-Ay小鼠的血浆和肝脏甘油三酯水平。总之,我们的研究结果表明,13-oxo-ODA作为一种有效的PPARα激动剂,表明有可能改善肥胖诱导的血脂异常和肝脂肪变性。
Dyslipidemia is a major risk factor for development of several obesity-related diseases. The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that regulates energy metabolism. Previously, we reported that 9-oxo-10,12-octadecadienoic acid (9-oxo-ODA) is presented in fresh tomato fruits and acts as a PPARα agonist. In addition to 9-oxo-ODA, we developed that 13-oxo-9,11-octadecadienoic acid (13-oxo-ODA), which is an isomer of 9-oxo-ODA, is present only in tomato juice. In this study, we explored the possibility that 13-oxo-ODA acts as a PPARα agonist in vitro and whether its effect ameliorates dyslipidemia and hepatic steatosis in vivo. In vitro luciferase assay experiments revealed that 13-oxo-ODA significantly induced PPARα activation; moreover, the luciferase activity of 13-oxo-ODA was stronger than that of 9-oxo-ODA and conjugated linoleic acid (CLA), which is a precursor of 13-oxo-ODA and is well-known as a potent PPARα activator. In addition to in vitro experiment, treatment with 13-oxo-ODA decreased the levels of plasma and hepatic triglycerides in obese KK-Ay mice fed a high-fat diet. In conclusion, our findings indicate that 13-oxo-ODA act as a potent PPARα agonist, suggesting a possibility to improve obesity-induced dyslipidemia and hepatic steatosis.
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