Metabolomics study of the effect of smoking and high-fat diet on metabolic responses and related mechanism following myocardial infarction in mice
Metabolomics study of the effect of smoking and high-fat diet on metabolic responses and related mechanism following myocardial infarction in mice
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吸烟和高脂饮食对小鼠心肌梗死后代谢反应影响及相关机制的代谢组学研究
DOI：
10.1016/j.lfs.2020.118570
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Chengxing Shen
中科院分区：
文献类型：
--
作者：
Zhe Zhao;Yaping Zhang;Liang Liu;Yu Chen;Di Wang;Xian Jin;Chengxing Shen
目的本研究旨在评价慢性吸烟和高脂饮食对心肌梗死后代谢特征和炎症消退的影响，主要方法将8周龄C57 BL/6 J小鼠随机分为对照组（C）、吸烟组（S）、高脂饮食组（H）和吸烟加高脂饮食组（SH），共16周。心肌梗死是由永久性冠状动脉结扎。在MI后5天通过超声心动图评估心脏功能。结果：SH组左心室短轴缩短率（FS%）和射血分数（EF%）均较S组和H组显著降低（P< 0.05），而S组和H组无显著差异（P> 0.05）。心肌代谢组学分析表明，在S、H和SH组中，分别有3、6和11条代谢途径被认为是最相关的途径（影响> 0.1）。三组中最常见的相关途径是花生四烯酸代谢。高脂饮食与吸烟相结合可加重心肌梗死后心功能不全，并引起炎症、能量代谢、氧化应激等代谢途径的紊乱。吸烟结合高脂饮食也可加重MI后炎症反应，影响MI小鼠炎症反应的消退。
AimsThe present study aimed to evaluate the impact of chronic smoking and high fat diet on the post-MI metabolic features and inflammation resolution.Main methodsEight weeks old C57BL/6J mice were randomly divided into control(C), smoking(S), high-fat diet(H), and smoking plus high-fat diet(SH) groups for 16 weeks. MI was induced by permanent coronary ligation. Cardiac function was assessed by echocardiography at 5 days post-MI. The infarcted heart tissue was collected for the metabolic profile using metabolomics and quantification of pro-resolving mediators with immunoblotting.Key findingsPercentage of fractional shortening (FS%) and ejection fraction (EF%) were further reduced in SH than that in either S or H group (P< 0.05). Myocardial metabolomics analysis indicated that 3, 6, and 11 disturbed metabolic pathways were considered as the most relevant pathway (Impact > 0.1) in S, H, and SH groups, respectively. The common most relevant pathway among three groups was arachidonic acid metabolism. The levels of arachidonic acid and TXB2 were significantly higher, while the 5-LOX and HO-1 expression was significantly lower in SH group than that in either S or H group (P< 0.05).SignificanceSmoking superimposed on high-fat diet could aggravate post-MI cardiac dysfunction and cause significant disturbance of metabolic pathways associated with inflammation, energy metabolism, as well as excessive oxidative stress. Smoking combined with high-fat diet could also magnify the post-MI inflammation and impair the resolution of inflammation in MI mice.