Recent evidence suggests that
cholesterol (Ch) solubility in bile is determined by a complex interaction of mixed
micelles and
lecithin-
cholesterol vesicles.
Bilirubin monoglucuronide (BMG), which binds to
bile salts and incorporates into mixed
micelles, may displace
cholesterol from
micelles into vesicles, thus favoring
cholesterol monohydrate crystal precipitation. Therefore, we designed an experiment to test the hypothesis that BMG may enhance
cholesterol gallstone formation without inducing
cholesterol supersaturation. For 8 weeks, 28 adult male prairie dogs were fed either a control, nonlithogenic diet (0.03% Ch), a high
carbohydrate diet (CHO) which has no
cholesterol but increases hepatic
bilirubin secretion, or the same CHO diet plus 0.03% Ch.
Cholecystectomy was then performed, and bile was examined microscopically for stones or crystals and analyzed for BMG and biliary
lipids.
Cholesterol saturation index was calculated.
Cholesterol gallstones were found in none of the control animals and in 13% of the CHO-fed animals. However, the addition of trace
cholesterol to the CHO diet resulted in an 88% incidence of
cholesterol gallstones (P less than 0.001 vs control, P less than 0.01 vs CHO, respectively). Gallbladder bile was unsaturated with
cholesterol in all groups. (control = 0.65 +/- 0.05, CHO = 0.46 +/- 0.05, CHO + 0.03% Ch = 0.70 +/- 0.03). CHO feeding alone or with trace
cholesterol significantly elevated gallbladder
bilirubin monoglucuronide,
phospholipid, and
cholesterol concentrations when compared to controls. These data suggest that in the prairie dog a high
carbohydrate diet with only trace amounts of
cholesterol increases
bilirubin monoglucuronide in gallbladder bile and causes
cholesterol gallstone formation without inducing
cholesterol supersaturation.(ABSTRACT TRUNCATED AT 250 WORDS)