Abstract

In order to study the mechanisms influencing bile acid pool size and cholesterol saturation index of fasting gall bladder bile, eight obese volunteers were placed on a low calorie diet for six weeks, and given intramuscular injections of a pharmacological dose of cholecystokinin octapeptide (CCK-OP, 5 micrograms) at mealtimes for half that period (alternating order). During CCK-OP administration, postprandial emptying of the gall bladder (mean +/- SEM) increased from 58 +/- 11% to 82 +/- 5% (p less than 0.005), and small intestinal transit time decreased from 205 +/- 27 to 178 +/- 26 minutes (NS). Bile acid pool size decreased from 4.6 +/- 0.3 to 3.1 +/- 0.3 mmol (p less than 0.001), while fractional turnover rate for chenodeoxycholic acid increased from 0.23 +/- 0.02 to 0.36 +/- 0.03 per day (p less than 0.005), suggesting an increase in recycling frequency of the pool. Synthesis rate was unchanged (0.43 +/- 0.08 vs 0.44 +/- 0.07 mmol/day), suggesting a new steady state. The cholesterol saturation index of fasting gall bladder bile increased in all subjects from 1.3 +/- 0.1 to 1.6 +/- 0.1 (p less than 0.005). Fasting gall bladder volume was reduced from 29 +/- 4 to 20 +/- 7 ml (p less than 0.01). Fractional turnover rate on the two regimens correlated with gall bladder emptying (n = 16, r = 0.61, p less than 0.01), but not with small intestinal transit time (r = 0.07, NS). Bile acid pool size correlated with fractional turnover rate (r = -0.73, p less than 0.005) and with cholesterol saturation index (r = -0.56, p less than 0.025). These findings suggest that CCK influences bile acid kinetics and cholesterol saturation index of fasting gall bladder in man; and that these effects of CCK are mainly mediated via alterations in gall bladder emptying rather than through alterations in small intestinal transit rate.