| Abstrakt: |
While exogenous administration of cholecystokinin (CCK) decreases food intake in many species, it has not been demonstrated conclusively that CCK is necessary for satiety to occur. In these experiments the role of CCK in eliciting satiety was further investigated by using endogenously produced and exogenously administered antibodies to CCK which were hypothesized to sequester circulating CCK. In the first experiment Zucker obese (n=12, 192±16 g) and lean (n=12, 152±11 g) male rats were administered CCK-8 conjugated to bovine serum albumin or bovine serum albumin by subcutaneous administration in Freund's adjuvant. Average percent binding of 125I-gastrin-17 by serum taken 4, 8 and 12 weeks after treatment initiation was increased (19.9 vs. 2.1, p<0.001) in rats treated with CCK conjugate than controls, and the increase was greater in lean (27.5 vs. 1.9) than in obese (12.2 vs. 2.2, p<0.001) rats. In lean, but not obese rats, average daily food intake and weight gain were increased (9 and 17% p<0.04 and p<0.02 respectively) in rats with CCK-AB compared with rats with no CCK-AB during the three months. Development of CCK-AB did not affect food intake response to exogenously administered CCK-8 or pancreas weight relative to body weight. In Experiment 2 increased food intakes of obese and lean rats 30 min after intraperitoneal injection of rabbit serum with CCK-AB were greater than those after intraperitoneal injection of rabbit serum without CCK-AB (1.92 vs. 1.41, g, p<0.007). Percent binding of serum from rats administered the same rabbit serum with CCK-AB intraperitoneally increased after 30 min (2.29 vs. 0.97, p<0.05). Thus, increased food intake may have been due to sequestering of free circulating CCK by the absorbed CCK-AB. In these experiments it is postulated that sequestering of CCK released during a meal increased the size of that meal; and in rats which developed endogenous CCK-AB, daily food intake and weight gain were increased, providing strong evidence that CCK plays a physiological role in satiety. The lack of response in obese rats with CCK-AB may be related to their decreased sensitivity to the effects of CCK on food intake and pancreas exocrine function. |
