Plasma lipidomics reveal profound perturbation of glycerophospholipids, fatty acids, and sphingolipids in diet-induced hyperlipidemia

- Hyperlipidemic model was performed by feeding rats with high fat diets.
- UPLC-HDMS-based lipidomic approach was applied to analysis of plasma lipids.
- Perturbation of GPs, fatty acids and sphingolipids were observed in model rats.
- This study indicated the perturbations of lipids metabolism in hyperlipidemic rat.

Hyperlipidemia is a major risk factor for coronary heart disease and has emerged as an important public health problem. Lipidomics is a powerful technology for assessment of global lipid metabolites in a biological system and for biomarker discovery. In the present study, hyperlipidemia was induced by feeding rats a high fat diet. A sensitive ultra-performance liquid chromatography coupled with quadrupole time-of-flight synapt high-definition mass spectrometry method was used for the analysis of plasma lipids. Orthogonal partial least squares-discriminant analysis, correlation analysis and heatmap analysis were performed to investigate the metabolic changes in rats with diet-induced hyperlipidemia. Potential biomarkers were detected using S-plot and were identified by accurate mass data, isotopic pattern and MSE fragments information. Significantly increased total cholesterol, triglycerides and low-density lipoprotein cholesterol as well as decreased high-density lipoprotein cholesterol were observed in diet-induced hyperlipidemic rats. Combined with standard serum biochemical results, significant differences in plasma lipid compounds including eleven glycerophospholipids, six fatty acids, two sphingolipids, one eicosanoid, one sterol lipid and one glycerolipid were observed, highlighting the perturbation of lipid metabolism in diet-induced hyperlipidemia. These findings provide further insights into the lipid profile across a wide range of biochemical pathways in diet-induced hyperlipidemia.

The base peak intensity chromatograms cover all the identified lipids from control and diet-induced hyperlipidemic rats. Biomarkers of black text were up-regulated in the diet-induced hyperlipidemic rats. Biomarkers of blue text were down-regulated in the chromatograms.