Diminished satiation in rats exposed to elevated levels of endogenous or exogenous cholecystokinin

Rats maintained on a high-fat (HF) diet exhibit reduced sensitivity to the satiation-producing effect of exogenous CCK. Because more CCK is released i n response to HF meals than low-fat (LF) meals, we hypothesized that increa sed circulating CCK associated with ingestion of HF diets contributes to th e development of decreased CCK sensitivity. To test this hypothesis, we imp lanted osmotic minipumps filled with either NaCl or CCK octapeptide into th e peritoneal cavity. Subsequently, we examined the effect of intraperitonea l NaCl or CCK (0.5 mug/kg) injection on 30-min food intake. CCK significant ly reduced 30-min food intake less in rats implanted with CCK-releasing min ipumps compared with those with NaCl-releasing minipumps. Because dietary p rotein is a potent releaser of endogenous CCK, we hypothesized that rats ad apted to a high-protein (HP) diet might also exhibit reduced sensitivity to exogenous CCK. Therefore, in a second experiment, we examined CCK-induced reduction of food intake in rats maintained on LF and rats maintained on HF or HP. Ingestion of LF stimulates very little endogenous CCK secretion, wh ereas both HF and HP markedly increase plasma CCK concentrations. Both dose s of CCK reduced food intake significantly less in HF and HP rats compared with LF rats. There were no differences in 24-h food intake, body weight, o r body fat composition among LF-, HF-, and HP-fed rats. These results are c onsistent with the hypothesis that sustained elevation of CCK either by inf usion of exogenous CCK or by dietary-induced elevation of plasma CCK contri butes to the development of reduced sensitivity to exogenous CCK.