Sea Cucumber Phospholipids Regulate Cholesterol Metabolism in High-Fat Diet-Induced ApoE−/− Mice

Sea cucumber phospholipids, marine-derived lipids with high nutritional functions, have been proven to exhibit various biological activities. However, it is unclear how sea cucumber phospholipids regulate cholesterol (Chol) metabolism in atherosclerosis.This study aimed to investigate the effects and mechanism of sea cucumber phospholipids on the metabolism of Chol and cholesterol esters (CE) in ApoE-/- mice, including plasmenyl phosphatidylethanolamine (PE-P) and plasmanyl phosphatidylcholine (PC-O).Male ApoE-/- mice were fed with Chow diet, high-fat diet (HFD), and HFD supplemented with PC-O or PE-P, respectively. We integrated a targeted lipidomics strategy to classify and compare the cholesteryl esters according to their fatty acid types, and then analyzed the individual cholesteryl ester molecular species in the liver and serum of mice. Furthermore, the Chol metabolism-related genes and pathways were analyzed in high-fat-induced ApoE-/- mice.Biochemical analysis showed that sea cucumber phospholipids significantly inhibit the generation of arterial plaque in ApoE-/- mice. Compared with the HFD group, PE-P significantly reduced the contents of SFA-CE and MUFA-CE in mice liver (P < 0.05), whereas PC-O particularly upregulated CE20:5 and CE22:6 in the serum of mice (P < 0.001). Furthermore, PC-O and PE-P inhibited the Chol synthesis pathway (Cyp7A1 and Cyp27A1), as well as promoted the catabolism of Chol by upregulating gene expressions of bile acid synthesis (Abcb11) and lysosomal activity (Lamp1), respectively.Sea cucumber phospholipids could ameliorate the atherosclerosis symptoms by regulating Chol metabolism. J Nutr 20xx;x:xx.