Abstract
Flax lignans (SDG) and sinapic acid (SA) both have the function of antioxidation and anti-inflammation. However, previous studies have focused mainly on biochemical measurements, gene expression analysis, and clinical assessments. There are limited studies that systematically reveal the underlying mechanism of the anti-inflammation effect of SDG or SA from the lipidomic point of view. Herein, the integrated lipidomic profiling platform was used for the analysis of free fatty acids (FFAs), phospholipids (PLs), triacylglycerols (TAGs), and oxylipins in high-fat (HF)-diet-fed mice after SDG or SA administration. Dietary supplementation of SDG or SA downregulated the levels of total TAGs and FFAs in the ApoE-/- mice model. Furthermore, 28 potential lipids were screened out and considered as key evaluation factors to understand the anti-inflammation function and mechanism of SDG and SA. The results indicated that the anti-inflammatory effect of SDG and SA was principally exerted via regulation of lipid homeostasis.
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Key Points
In this paper, a comprehensive integrated lipidomic profiling platform was used for the analysis of free fatty acid (FFA), phospholipids (PLs), triacylglycerols (TAGs), and oxylipins in HF-diet-fed ApoE−/− mice after SDG or SA administration. Via qualitative and quantitative lipidomic analysis and statistical analysis in mice serum from different intervention groups, the effect of functional SDG and SA inflammation was evaluated at the molecular level.
In this study, an increase of TAG and FFA levels was detected in the HF group, implying a successful inflammatory dyslipidemia model in ApoE−/− mice. Hierarchical clustering dendrograms were conducted, and the result suggested that SDG might be more effective than SA in anti-inflammation. Further, metabolic pathway analysis of these potential differential lipidomic metabolites suggested that disturbance of LA metabolism was among the most significantly altered metabolic pathway after SDG and SA administration in HF-diet-fed ApoE−/− mice. After dietary intervention with SA or SDG, the main impacted pathways of AA metabolism changed into LA metabolism and the p value and the pathway impact were the highest in the HF-L group after intervention with SDG.
A total of 28 potential lipids were investigated as evaluation factors to understand the anti-inflammation function and mechanism of SDG and SA. Through lipidomic, pathway, and statistical analyses in mice serum, SA and SDG are proven to have anti-inflammatory effects. From statistical and pathway analysis results, the anti-inflammatory functional effect of SDG might be better than that of SA. These findings indicated that the regulation of lipid homeostasis might be the key factor for the mechanism of SDG and SA underlying the anti-inflammatory effect.