Investigating the Effects and Mechanism of Phytosterols in Reducing Liver Cholesterol in L02 Cells and Golden Hamsters

ABSTRACT

This study examines the cholesterol‐lowering effects of soybean sterols (SS) in L02 cells and hamsters via SREBP‐2/LXRα. Methods: Using L02 cells and hamsters as research subjects, we conducted an analysis on the impact of soybean sterols (SS) on the assimilation, synthesis, and elimination of cholesterol from hepatic cells. Through metabolomic profiling, we aimed to elucidate the mechanism by which soybean sterols lower cholesterol levels. Results: SS orchestrated a reduction in total cholesterol (TC) and triglyceride (TG) levels through the regulation of genes associated with cholesterol absorption and biosynthesis in L02 cells. In hamsters, SS supplementation led to a dosage‐dependent decrease in TC and free cholesterol (FC) in serum and livers. Furthermore, the potential mechanism underlying SS‐induced cholesterol lowering may involve modulation of metabolites such as StE (22:6), PE (29:1/18:2), and ZyE (18:3). Interestingly, it was found that SS had a minimal impact on TG levels, but excessive SS led to an increase in TG levels. Conclusions: The discoveries underscore the advantageous influence of phytosterols on hepatic cholesterol metabolism; however, given the effects of phytosterols on TG, caution should be exercised in the intake dosage. This research lays down a fundamental cornerstone for the prevention and treatment of elevated cholesterol levels.

Practical Application : This study provides a mechanistic basis for the cholesterol‐lowering benefits of soybean‐derived phytosterols, demonstrating their direct role in regulating hepatic cholesterol synthesis and excretion. The findings support the inclusion of phytosterols in functional foods or dietary supplements for managing hypercholesterolemia. However, the observed dose‐dependent effect on triglycerides—with the highest dose increasing TG levels—serves as a critical translational caution. It underscores that while phytosterols are effective for cholesterol reduction, excessive intake beyond recommended dietary guidelines (approximately 2 g/day in humans) may have unintended metabolic consequences. This research informs both the development of phytosterol‐enriched products and the establishment of safe intake recommendations for cardiovascular health promotion.