Comparison of the hepatic clearances of campesterol, sitosterol, and cholesterol in healthy subjects suggests that efflux transporters controlling intestinal sterol absorption also regulate biliary secretion

Abstract

Background: Recently identified ABCG5/8 transporters are responsible in part for the different absorption rates of campesterol, sitosterol, and cholesterol. These transporters are also expressed in the liver and might regulate biliary sterol secretion. Aims: This study was therefore conducted to determine the biliary secretion rates and hepatic clearances of campesterol, sitosterol, and cholesterol. Subjects: Six healthy, male volunteers. Methods: Deuterium labelled sitosterol and campesterol, and unlabelled sitostanol were constantly infused together with a liquid formula using a duodenal perfusion technique. Biliary secretion and hepatic clearance rates were calculated from hourly bile and plasma samples. Results: Plasma concentrations of cholesterol, campesterol, and sitosterol averaged 167.5 (50) mg/dl (SD), 0.50 (0.22) mg/dl, and 0.30 (0.10) mg/dl, respectively. Sitosterol showed a significantly higher biliary secretion rate (1.23 (0.87) mg/h) than campesterol (0.76 (0.54) mg/h, p=0.0321), but both plant sterols had significantly lower biliary secretion rates compared with cholesterol (47.7 (17.5) mg/h; p=0.001 for both). Hepatic clearance of cholesterol (0.31 (0.18) dl/h) was significantly lower compared with campesterol (2.11 (2.51) dl/h) and sitosterol (4.97 (4.70) dl/h; p=0.028 for both), and the clearance of campesterol was significant lower compared with sitosterol (p=0.028). Conclusion: The observed inverse relation between hepatic clearance and known intestinal absorption of cholesterol, campesterol, and sitosterol supports the hypothesis that the ABCG5/8 transporters regulating intestinal sterol absorption might also be involved in biliary sterol excretion.

Dysregulation of distal cholesterol biosynthesis in association with relapse and advanced disease in CHC genotype 2 and 3 treated with sofosbuvir and ribavirin

“…Although these dietary phytosterols contribute to an insignificant proportion of the total cholesterol pool, they are surrogate markers for intestinal cholesterol absorption [51], and have not been previously evaluated in HCV infection. Sterol absorption is regulated by intestinal transporters, and since we observed an increase in phytosterols campesterol and sitosterol in GT3 patients at TW12, this suggests possible viral inhibition of intestinal efflux and biliary transporters [52]. Our observation also reflects change in cholesterol biosynthesis with therapy in GT3 patients, that likely influences cholesterol absorption to maintain relative lipid homeostasis.…”

Dose-response effects of different plant sterol sources in fat spreads on serum lipids and C-reactive protein and on the kinetic behavior of serum plant sterols

“…Campesterol excretion is estimated to be at least 2 mg/day based on the abovementioned single-dose studies, but is probably 60 mg/day in our studies over the first 2 weeks based on the probable absorbed dose and the t 1/2 of 2 weeks. Sudhop et al (2002) measured a clearance rate of 1.23 mg/h for sitosterol and 0.76 mg/h for campesterol with a 9 h intestinal infusion and bile collection. In our study, calculated clearance rates of sitosterol and campesterol are the same and not dependent on the PS source.…”

Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal

“…Campesterol appears to be absorbed to a greater degree than sitosterol as the amount in the phytosterol margarine is about half of the sitosterol level, while the increase in plasma is about twice. However, altered hepatic clearance may also account for this difference (Sudhop et al, 2002).…”