High‐Fat Diet Attenuates the Benefits of Increasing Phospholipid‐to‐Cholesterol Ratio on Lipid Metabolism in Mice: Evidence From Egg Yolk Low‐ and High‐Density Lipoprotein Intake

ABSTRACT Our previous study suggested that increasing the phospholipid‐to‐cholesterol intake ratio might mitigate the negative effects of cholesterol intake, based on a comparison of lipid metabolism changes in mice fed chow diets containing egg yolk low‐density lipoprotein (LDL) and high‐density lipoprotein (HDL). This benefit might stem from the involvement of phospholipids, leading to reduced food efficiency, decreased body weight, and increased bile acid excretion. In this study, we further investigated the effects of this ratio on lipid metabolism under a high‐fat diet (HFD) using egg yolk LDL and HDL, which differ in the proportions of phospholipids and cholesterol. Both LDL and HDL intake led to increased body weight and adipose tissue weight in mice, with significant effects observed in the HFD‐LDL3 group. Accordingly, these groups exhibited overall increases in food efficiency. Lipid biomarkers indicated that both LDL and HDL intake significantly elevated plasma and liver triglyceride (TG) levels. Cholesterol in the blood might be stored with TGs in adipose tissue. No significant differences were observed in lipid biomarkers between the HFD‐LDL and HFD‐HDL groups under the same cholesterol dose. Western blot results showed upregulated cholesterol synthesis following LDL and HDL intakes. Bile acid excretion also increased, though not significantly. Fecal metabolite analysis further revealed changes in polyunsaturated fatty acids, pregnane‐type steroids, and bile acids. Compared to our previous findings, increasing the phospholipid‐to‐cholesterol intake ratio under an HFD had a weaker beneficial effect on lipid metabolism than under a chow diet, possibly due to the lower proportion of phospholipids in the total lipids.