Torularhodin-Loaded Bilosomes Ameliorate Lipid Accumulation and Amino Acid Metabolism in Hypercholesterolemic Mice

Scope: Hypercholesterolemia is a cause of cardiovascular disease. Torularhodin is a carotenoid, and its entrapment in bilosomes helps to improve its bioavailability. Methods and results: The effects of torularhodin-loaded bilosomes on lipid accumulation, inflammatory response, and serum metabolic profiles in hypercholesterolemic ApoE–/– C57BL/6J mice were investigated by feeding a high-fat, high-cholesterol diet (HFHCD) for 20 weeks. At the same time, mice were gavaged with torularhodin-loaded bilosomes for 10 weeks. The results showed that torularhodin successfully alleviated weight gain and insulin resistance in mice and could also lower blood lipids. Meanwhile, torularhodin improved liver lipid accumulation in mice and modulated inflammatory factors in the “blood–liver–ileum.” Nontargeted metabolomics revealed that torularhodin significantly increased the concentrations of l -tryptophan, glyceraldehyde, hypotaurine, pyrophosphate, and niacinamide in serum ( p < 0.01). In addition, targeted amino acid metabolomics verification found that torularhodin promoted the metabolism of serum amino acids in mice, particularly for branched-chain amino acids, thereby helping to improve hypercholesterolemia in mice. Finally, interaction network bioinformatics was used to demonstrate that amino acid metabolism represented an important mechanism by which torularhodin improves lipid accumulation and inflammatory response in mice. Conclusions: Torularhodin can improve hypercholesterolemia in HFHCD-fed mice, thereby supporting the feasibility of its usage in food applications for cardiovascular disease prevention.