Quercetin ameliorates dysregulation of lipid metabolism genes via the PI3K/AKT pathway in a diet-induced mouse model of nonalcoholic fatty liver disease
Quercetin ameliorates dysregulation of lipid metabolism genes via the PI3K/AKT pathway in a diet-induced mouse model of nonalcoholic fatty liver disease
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DOI：
10.1002/mnfr.201400913
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发表时间：
2015-05-01
影响因子：
5.2
通讯作者：
Sanchez-Campos, Sonia
中科院分区：
文献类型：
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作者：
Pisonero-Vaquero, Sandra;Martinez-Ferreras, Angel;Sanchez-Campos, Sonia
适用范围：黄酮类化合物和相关化合物似乎对非酒精性脂肪性肝病（NAFLD）的进展有有利的影响，尽管涉及的确切机制知之甚少。在这项研究中，我们的目的是调查的flanovol槲皮素对基因表达失调参与NAFLD的发展，以及磷脂酰肌醇3-激酶（PI 3 K）/AKT通路modulation.Methods和结果的可能含义：我们使用了体内模型的基础上蛋氨酸和胆碱缺乏（MCD）饮食喂养的小鼠和体外模型组成的Huh 7细胞与MCD培养基孵育。喂食MCD的小鼠表现出非酒精性脂肪性肝炎的典型病理生理学特征，与脂肪酸摄取和转运相关基因表达的转录调节改变相关，并伴有脂质过氧化增加。通过与PI 3 K抑制剂LY 294002一起孵育细胞，证明PI 3 K/AKT途径被MCD激活并触发基因失调，导致所有研究基因的激活或抑制。槲皮素治疗减少AKT磷酸化，氧化/亚硝化应激，炎症和脂质代谢相关基因表现出一种趋势，在体内和体外models.Conclusion正常化：这些结果放置槲皮素作为一个潜在的治疗策略，通过衰减基因表达失调，至少部分通过PI 3 K/AKT通路失活，以防止NAFLD进展。
Scope: Flavonoids and related compounds seem to have favorable effects on nonalcoholic fatty liver disease (NAFLD) progression, although the exact mechanisms implicated are poorly understood. In this study, we aimed to investigate the effect of the flanovol quercetin on gene expression deregulation involved in the development of NAFLD, as well as the possible implication of phosphatidylinositol 3-kinase (PI3K)/AKT pathway modulation.Methods and results: We used an in vivo model based on methionine-and choline-deficient (MCD) diet-fed mice and an in vitro model consisting of Huh7 cells incubated with MCD medium. MCD-fed mice showed classical pathophysiological characteristics of nonalcoholic steatohepatitis, associated with altered transcriptional regulation of fatty acid uptake-and trafficking-related gene expression, with increased lipoperoxidation. PI3K/AKT pathway was activated by MCD and triggered gene deregulation causing either activation or inhibition of all studied genes as demonstrated through cell incubation with the PI3K-inhibitor LY294002. Treatment with quercetin reduced AKT phosphorylation, and oxidative/nitrosative stress, inflammation and lipid metabolism-related genes displayed a tendency to normalize in both in vivo and in vitro models.Conclusion: These results place quercetin as a potential therapeutic strategy for preventing NAFLD progression by attenuating gene expression deregulation, at least in part through PI3K/AKT pathway inactivation.