Hydroxyeicosapentaenoic acids and epoxyeicosatetraenoic acids attenuate early occurrence of nonalcoholic fatty liver disease
Hydroxyeicosapentaenoic acids and epoxyeicosatetraenoic acids attenuate early occurrence of nonalcoholic fatty liver disease
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羟基二十碳五烯酸和环氧二十碳四烯酸可减轻非酒精性脂肪肝疾病的早期发生。
DOI：
10.1111/bph.13844
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发表时间：
2017
影响因子：
7.3
通讯作者：
Ai Ding
中科院分区：
文献类型：
--
作者：
Wang Chunjiong;Liu Wenli;Yao Liu;Zhang Xuejiao;Zhang Xu;Ye Chenji;Jiang Hongfeng;He Jinlong;Zhu Yi;Ai Ding
背景与目的ω-3多不饱和脂肪酸（PUFAs）对多种代谢紊乱具有保护作用。然而，它们的代谢产物在非酒精性脂肪性肝病（NAFLD）早期阶段的功能在很大程度上是未知的。实验方法小鼠被喂食对照饮食、高脂饮食（HFD）或富含ω-3 PUFA的HFD（ω 3 HFD）4天，并分析表型。LC-MS/MS用于确定类花生酸谱。原代肝细胞和腹腔巨噬细胞被用于机制study.Key ResultsIn短期HFD喂养的小鼠，肝脏中显著增加的脂质积累被ω-3 PUFA补充逆转。代谢组学显示，短期HFD降低了羟基二十碳五烯酸（HEPE）和环氧二十碳四烯酸（EEQ）的血浆浓度，ω 3 HFD显著升高。然而，HEPE/EEQ处理对肝细胞没有直接的保护作用。ω 3 HFD还显着减弱了HFD诱导的脂肪组织炎症。此外，巨噬细胞中的HEPE和EEQ抑制了棕榈酸酯诱导的促炎细胞因子的表达和JNK通路的激活。17，18-EEQ、5-HEPE和9-HEPE被确定为这些代谢物中的有效成分，这表明与巨噬细胞中的其他代谢物相比，它们对棕榈酸酯诱导的炎症因子表达、趋化性和JNK活化的抑制作用更大。结论：17，18-EEQ、5-HEPE和9-HEPE可通过JNK信号通路抑制脂肪组织巨噬细胞的炎症反应，从而在早期预防NAFLD。
Background and PurposeThe ω‐3 polyunsaturated fatty acids (PUFAs) mediate protective effects on several metabolic disorders. However, the functions of their metabolites in the early stage of nonalcoholic fatty liver disease (NAFLD) are largely unknown.Experimental ApproachMice were fed a control diet, high‐fat diet (HFD) or ω‐3 PUFA‐enriched HFD (ω3HFD) for 4 days and phenotypes were analysed. LC–MS/MS was used to determine the eicosanoid profiles. Primary hepatocytes and peritoneal macrophages were used for the mechanism study.Key ResultsIn short‐term HFD‐fed mice, the significantly increased lipid accumulation in the liver was reversed by ω‐3 PUFA supplementation. Metabolomics showed that the plasma concentrations of hydroxyeicosapentaenoic acids (HEPEs) and epoxyeicosatetraenoic acids (EEQs) were reduced by a short‐term HFD and markedly increased by the ω3HFD. However, HEPE/EEQ treatment had no direct protective effect on hepatocytes. ω3HFD also significantly attenuated HFD‐induced adipose tissue inflammation. Furthermore, the expression of pro‐inflammatory cytokines and activation of the JNK pathway induced by palmitate were suppressed by HEPEs and EEQs in macrophages. 17,18‐EEQ, 5‐HEPE and 9‐HEPE were identified as the effective components among these metabolites, as indicated by their greater suppression of the palmitate‐induced expression of inflammatory factors, chemotaxis and JNK activation compared to other metabolites in macrophages. A mixture of 17,18‐EEQ, 5‐HEPE and 9‐HEPE significantly ameliorated the short‐term HFD‐induced accumulation of macrophages in adipose tissue and hepatic steatosis.Conclusion and Implications17,18‐EEQ, 5‐HEPE and 9‐HEPE may be potential approaches to prevent NAFLD in the early stage by inhibiting the inflammatory response in adipose tissue macrophages via JNK signalling.