8-Hydroxyeicosapentaenoic Acid Decreases Plasma and Hepatic Triglycerides via Activation of Peroxisome Proliferator-Activated Receptor Alpha in High-Fat Diet-Induced Obese Mice
8-Hydroxyeicosapentaenoic Acid Decreases Plasma and Hepatic Triglycerides via Activation of Peroxisome Proliferator-Activated Receptor Alpha in High-Fat Diet-Induced Obese Mice
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DOI：
10.1155/2016/7498508
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发表时间：
2016-01-01
影响因子：
5.3
通讯作者：
Hirose, Masamichi
中科院分区：
文献类型：
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作者：
Yamada, Hidetoshi;Kikuchi, Sayaka;Hirose, Masamichi
PPARs调节参与脂质稳态的基因的表达。PPARs作为脂肪酸的分子传感器，它们的激活可以对抗肥胖和代谢综合征。8-羟基二十碳五烯酸（8-HEPE）作为一种过氧化物酶体增殖物激活受体配体，具有比EPA更高的活性。然而，迄今为止，仅在体外证明了8-HEPE的PPAR配体活性。在此，我们通过检查8-HEPE治疗对高脂饮食诱导的小鼠肥胖症的影响来研究其体内配体活性。4周治疗期后，8-HEPE喂养小鼠的血浆和肝脏甘油三酯水平显著低于HFD喂养小鼠。与仅接受HFD的小鼠相比，8-HEPE喂养的小鼠中受PPAR α调控的基因表达显著增加。此外，8-HEPE喂养小鼠的肝棕榈酸水平显著低于HFD喂养小鼠。这些结果表明，摄入8-HEPE可诱导PPAR α激活并增加肝脏中脂质的分解代谢。我们发现EPA喂养的小鼠和HFD喂养的小鼠之间没有显著差异。我们证明了8-HEPE对代谢综合征的积极作用大于EPA，并且8-HEPE通过诱导肝脏中的PPAR α活化而起作用。
PPARs regulate the expression of genes involved in lipid homeostasis. PPARs serve as molecular sensors of fatty acids, and their activation can act against obesity and metabolic syndromes. 8-Hydroxyeicosapentaenoic acid (8-HEPE) acts as a PPAR ligand and has higher activity than EPA. However, to date, the PPAR ligand activity of 8-HEPE has only been demonstrated in vitro. Here, we investigated its ligand activity in vivo by examining the effect of 8-HEPE treatment on high fat diet-induced obesity in mice. After the 4-week treatment period, the levels of plasma and hepatic triglycerides in the 8-HEPE-fed mice were significantly lower than those in the HFD-fed mice. The expression of genes regulated by PPAR alpha was significantly increased in 8-HEPE-fed mice compared to those that received only HFD. Additionally, the level of hepatic palmitic acid in 8-HEPE-fed mice was significantly lower than in HFD-fed mice. These results suggested that intake of 8-HEPE induced PPAR alpha activation and increased catabolism of lipids in the liver. We found no significant differences between EPA-fed mice and HFD-fed mice. We demonstrated that 8-HEPE has a larger positive effect on metabolic syndrome than EPA and that 8-HEPE acts by inducing PPAR alpha activation in the liver.