High-phytosterol rapeseed oil prevents atherosclerosis by regulating liver lipid metabolism and intestine microbiota in ApoE^−/− mice

Atherosclerosis (AS) is a worldwide disease caused by disorders of lipid metabolism, and lipid deposition in artery walls. The study aims to evaluate the effect of high-phytosterol rapeseed oil (HPRO) on the prevention of AS and elucidate the mechanism involved by exploring the composition of liver lipids, lipid synthesis, and metagenomes. The results show that HPRO reduces dyslipidemia and lipid accumulation in mice, and prevents AS lesions. By liver lipidomics analysis, we found that HPRO prevents AS by regulating the pathways of lipid and atherosclerosis, and glycerolipid metabolism. HPRO was shown to down-regulate the protein expression level of liver lipid synthesis markers sterol regulatory element-binding protein 1 and fatty acid synthase via AMP-activated protein kinase, and this is superior to that of β-sitosterol. Through metagenomic analysis, we found that HPRO increased the levels of beneficial bacteria Bacillota and Muribaculaceae while decreasing the levels of harmful bacteria Enterobacterales and Pseudomonadota. Interestingly, correlation analysis of liver lipids, intestinal flora, and AS indicators found significant correlations among them.