In this study, we compare the distribution of intraperitoneally injected sitosterol, 7beta-hydroxysitosterol or vehicle only (control) for 28days in male ApoE-/- mice. Furthermore we examine its impact on surrogate markers of cholesterol biosynthesis and sterol absorption rate in plasma, brain and liver tissues from these animals. Injection of sitosterol revealed a 32.1% (P=0.013) lower plasma total cholesterol compared with control. Cholesterol corrected plasma and absolute brain and liver levels of sitosterol are 4.1-, 1.7-, and 7.2-fold (P<0.001 for all) higher, respectively. This is in accordance with a reduced plasma campesterol to cholesterol ratio (-16.2%; P=0.018) together with a 24.1% (P=0.047) lower concentration of hepatic lathosterol. After injection of 7beta-hydroxysitosterol the concentrations of 7beta-hydroxysitosterol in plasma, brain and liver are 21.0-, 65.8- and 42.7-fold (P<0.001 for all) higher, respectively, compared with control. Injection of 7beta-hydroxysitosterol revealed significantly lower plasma cholesterol corrected cholestanol and campesterol (-44.2%; P=0.001 and -24.5; P=0.004) as well as lower absolute liver cholestanol levels (-31.9%; P<0.001) compared with control. Intraperitoneally injected sitosterol and 7beta-hydroxysitosterol differently influence cholesterol metabolism in plasma and liver. We conclude that the polar 7beta-hydroxysitosterol compound can pass the blood brain barrier with higher efficacy than its substrate, sitosterol. Though present in higher amounts in the brain, both, sitosterol and 7beta-hydroxysitosterol do not influence cholesterol metabolism in the brain as proven by our surrogate markers.
Schött, H. F., Husche, C., Friedrichs, S., Miller, C. M., McCarthy, F. O., Laufs, U., Plat, J., Weingartner, O., & Lutjohann, D. (2015). 7beta-Hydroxysitosterol crosses the blood-brain barrier more favored than its substrate sitosterol in ApoE-/- mice. Steroids, 99B, 178-182. https://doi.org/10.1016/j.steroids.2015.03.006