Key result
High-fat diet drives plaque progression and alters hepatic and plasma lipidomes in mice.
Why the study?
Atherosclerosis is driven by lipid disorders from aberrant liver metabolism and release of lipids into the bloodstream, yet limited information existed regarding alterations in liver and blood lipid metabolism.
Does a high-fat diet alter the liver and plasma lipid profile and atherosclerotic lesion characteristics compared to a normal diet in ApoE −/− mice?
RCT
Randomly divided
Does a high-fat diet alter the liver and plasma lipid profile and atherosclerotic lesion characteristics compared to a normal diet in ApoE −/− mice?
This preclinical study identifies 11 distinct lipids (particularly PC and TG) differentially expressed in both the liver and plasma of high-fat diet-fed ApoE −/− mice, offering potential biomarkers and insights into the molecular mechanisms of atherosclerosis.
Highlights candidate lipid biomarkers in mouse atherosclerosis; leaves open human validation and clinical translation.
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.
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Zhang et al. (2026) conducted an RCT in Atherosclerosis and hepatic steatosis (ApoE−/− mice). High-fat diet (HFD) vs. Normal diet (ND) was evaluated on Liver and plasma lipid profile alterations and atherosclerotic plaque/lipid deposition. High-fat diet in ApoE−/− mice increased plaque area and lipid deposition, yielding 40 hepatic and 177 plasma differential lipids (11 overlapping) vs normal diet.
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