Two effects of high-fat diets on the satiating potency of cholecystokinin-8

Chronic ingestion of diets containing 34% or 54% fat have been reported [Peptides 19 (1998) 1407] to decrease the inhibitory effect on food intake of doses of cholecystokinin-8 (CCK-8) less than 1 μg/kg ip. We attempted to replicate this phenomenon in three experiments by comparing the effect of high-fat and low-fat diets on the threshold dose of CCK-8 for inhibition and on the dose-response function for doses of CCK-8 that ranged from 0.125 to 2.0 μg/kg. The first experiment tested rats five times per week. Rats on a 34% fat diet had a higher threshold (1.0 μg/kg) than rats on a 5% fat diet (0.25 μg/kg). The dose-response functions, however, were not significantly different. This result replicated the earlier report [Peptides 19 (1998) 1407]. The second experiment tested rats maintained on the same diets every other day as in the original report. It failed, however, to replicate the results of the first experiment or the earlier report because the threshold doses and the dose-response functions of CCK-8 were not significantly different between rats on 34% and 5% fat diets. The third experiment compared the potency of CCK-8 in rats on a 60% fat diet with the potency in rats on a 5% fat diet. CCK-8 was significantly more potent in the rats on the 60% fat diet because the threshold dose of these rats was lower (0.125 μg/kg) than in rats on the 5% fat diet (0.25 μg/kg), and the dose-response function in rats on the 60% fat diet was significantly more potent than in rats on the 5% fat diet. Thus, we observed two effects of the chronic ingestion of high-fat diets on the inhibitory potency of CCK-8: (1) A 34% fat diet increased the threshold dose of CCK-8 without changing the dose-response function in one of two experiments. (2) A 60% fat diet increased the potency of CCK-8 because it decreased the threshold dose and increased the dose-response function significantly.