Metabolomics study of the effect of smoking and high-fat diet on metabolic responses and related mechanism following myocardial infarction in mice

Abstract

Aims: The present study aimed to evaluate the impact of chronic smoking and high fat diet on the post-MI metabolic features and inflammation resolution.

Main methods: Eight 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 findings: Percentage 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).

Significance: Smoking 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.

Keywords: High fat diet; Metabolomics; Myocardial infarction; Resolution of inflammation; Smoking.