Distribution of cholesterol among its carriers in the bile of male and female hamsters

The distribution of cholesterol among its carriers was studied in the bile of male and female hamsters. Sasco hamsters (Sasco Inc., Omaha, NE) were fed a semipurified diet with 0.0% cholesterol and 4% butterfat (group 1, males; group 4, females); a semipurified diet with 0.3% cholesterol and 1.2% plamitic acid (group 2, males; group 5, females); and a semipirified diet with 0.3% cholesterol and 4% safflower oil (group 3, males; group 6, females). At the end of six weeks, gallstones were found only in male hamsters receiving both cholesterol and dietary fat (fatty acid) (incidence of cholesterol stones: 90% in group 2; 22% in group 3). The biliary cholesterol carriers were separated and isolated from the bile of the hamsters by gel filtration chromatography, using the method of Pattinson [Pattinson, N.R., Willis, K.E., and Frampton, C.M. (1991)J. Lipid Res. 32, 205–214]. In those male hamsters that formed cholesterol gallstones, significant amounts of cholesterol were present in the void volume which contained large cholesterol phospholipid vesicles (void volume vesicles) (23% in group 2 and 15% in group 3). Smaller cholesterol/phospholipid vesicles were eluted next (fractions 30–45) and contained 15% of biliary cholesterol in group 2 and 21% in group 3. The remainder of the cholesterol was associated with mixed cholesterol/phospholipid/bile salt micelles. The cholesterol/phospholipid ratio was larger in both the void volume vesicles and small vesicles (2.40 and 1.48 in group 2; 2.56 and 1.33 in group 3, respectively) compared to the micelles (about 0.3 in groups 2 and 3). In contrast, the bile of the female hasmters contained few vesicles (3% small vesciles in group 5) and the cholesterol/phospholipid ratio of these vesicles was lower (0.94). Hamsters fed cholesterol-free diets (groups 1 and 4) had no biliary cholesterol/phospholipid vesilces; and cholesterol was present in micelles. The results suggest that both the gender and the diet of the hamsters affected the distribution of biliary cholesterol between vesicles and micelles. The development of cholelithiasis in this animal model appears to depend on the rapid nucleation of cholesterol-rich phospholipid vesicles in bile.