Atherosclerosis (AS) is the most common cardiovascular disease (CVD). Currently, it is widely believed that R-TFA and I-TFA may cause different biological effects. In the present study, we aim to elucidate the effect of mixed R-TFA derived from butter on the development of AS in high-fat diet-fed ApoE–/– mice and find the possible mechanism. It was shown that butter-derived R-TFA promoted dyslipidemia, reduced thoracic and abdominal aorta diameters, and induced aortic lipid deposition and atherosclerotic lesions in high-fat diet-fed ApoE–/– mice. Meanwhile, butter-derived R-TFA affected the serum lipid profile of high-fat diet-fed ApoE–/– mice and the lipid metabolism of human umbilical vein endothelial cells (HUVECs). Through lipidomic techniques, we found that butter-derived R-TFA had a significant effect on the glycerophospholipid metabolic pathway. In conclusion, our results demonstrated that butter-derived R-TFA does not alleviate but promotes atherosclerotic lesions in high-fat diet-fed ApoE–/– mice and that the glycerophospholipid metabolic pathway plays a major role in this pro-atherosclerotic effect.

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