Plasma oxyphytosterols most likely originate from hepatic oxidation and subsequent spill-over in the circulation

We evaluated oxyphytosterol (OPS) concentrations in plasma and various tissues of two genetically modified mouse models with either increased cholesterol (apoE KO mice) or increased cholesterol and plant sterol (PS) concentrations (apoExABCG8 dKO mice). Sixteen female apoE KO and 16 dKO mice followed the same standard, low OPS-chow diet. Animals were euthanized at 36 weeks to measure PS and OPS concentrations in plasma, brain, liver and aortic tissue. Cholesterol and oxysteml (OS) concentrations were analyzed as reference for sterol oxidation in general. Plasma campesterol (24.1 +/- 4.3 vs. 11.8 +/- 3.0 mg/dL) and sitosterol (67.4 +/- 12.7 vs. 4.9 +/- 1.1 mg/dL) concentrations were severely elevated in the dKO compared to the apoE KO mice (p < 0.001). Also, in aortic and brain tissue, PS levels were significantly elevated in dKO. However, plasma, aortic and brain OPS concentrations were comparable or even lower in the dKO mice. In contrast, in liver tissue, both PS and OPS concentrations were severely elevated in the dKO compared to apoE KO mice (sum OPS: 7.4 +/- 1.6 vs. 4.1 +/- 0.8 ng/mg, p < 0.001). OS concentrations followed cholesterol concentrations in plasma and all tissues suggesting ubiquitous oxidation. Despite severely elevated PS concentrations, OPS concentrations were only elevated in liver tissue, suggesting that OPS are primarily formed in the liver and plasma concentrations originate from hepatic spill-over into the circulation.

Automated summary

In this study, we evaluated the concentrations of oxyphytosterol (OPS) in plasma and various tissues of two genetically modified mouse models. The findings showed that while the levels of plant sterols (PS) were significantly elevated in the plasma of the dKO mice, the concentrations of OPS were comparable or even lower. This suggests that OPS are primarily formed in the liver and their presence in plasma is due to spill-over from the liver.