Lipidomics Analysis Reveals That Lipid Profile Is Associated With the Liver and Plasma in ApoE ^−/−

ABSTRACT

The key pathogenesis of atherosclerosis is lipid disorders resulting from aberrant liver metabolism and release of lipids into the bloodstream, leading to endothelial damage and deposition of lipids beneath the endothelial layer. Currently, there exists a limited amount of information pertaining to alterations in liver and blood lipid metabolism. This study aimed to examine the lipid profile associated with the liver and plasma of ApoE ^−/− mice. ApoE ^−/− mice were selected because one high‐fat dietary challenge produces aortic lesions and hepatic steatosis in the same animal, allowing plaque and hepatic lipid disturbance to be sampled together. Mice were randomly divided into a normal diet (ND) group and a high‐fat diet (HFD) group. To validate the atherosclerosis model, histopathologic analysis techniques such as HE stain, Oil Red O stain, and Masson stain were employed. The lipid profile in both liver and plasma was evaluated using UHPLC‐Q Exactive plus MS, utilizing positive and negative ionization modes. In comparison to the ND group, the HFD group exhibited elevated levels of lipid deposition, plaque area, and collagen fiber. Specifically, the liver contained 40 distinct lipids, while the plasma contained 177 distinct lipids. Further examination demonstrated that 11 distinct lipids exhibited differential content in both the liver and plasma. This study demonstrated the existence of a comprehensive lipid profile in the liver and plasma of atherosclerotic mice, with a particular emphasis on PC and TG, which may provide a new biomarker and a better understanding of the molecular mechanisms underlying atherosclerosis.