EFFECTS OF CHOLECYSTOKININE ANALOGUE (JMV 236) ON PLASMA NPY IN OBESE RATS

Neuropeptide Y (NPY), involved in the enhancement of feeding behaviour, may vary according to the nutritional or ponderal status and by treatment with satiety-inducing substances, such as cholecysto-kinin (CCK). In this study, plasma NPY levels were measured using a radioimmunometric assay after treatment with a potent CCK peptide agonist in obese Zucker and ‘’cafeteria" rats. In the Zucker strain, basal NPY levels did not differ between the obese (fa-fa), lean heterozygote (Fa-fa) and lean homozygote (Fa-Fa) rats. However, the CCK agonist decreased NPY levels in the lean Fa-Fa rats only. This decrease could be expected given the opposite roles of NPY and CCK in the control of food intake. Similarly with other paradigms, the lean rats were more sensitive than the obese rats (fa-fa) of CCK peptides. Furthermore, the obese and Fa-fa rats were" irresponsive to the CCK agonist, suggesting that certain disturbances may be related to the presence of the ‘’fa’’ gene. The ‘’cafeteria’’ rat showed lower basal NPY levels compared to its lean congener. This mighnt be related to its constant hyperphagia, since NPY levels have been shown to increase during fasting and to decrease during refeeding. The CCK agonist decreased NPY levels in a significant manner in the ‘’cafeteria’’ rat. Thus, contrary to the obese Zucker rat, this model is more sensitive to the effects of CCK peptides. This study allows to differentiate the ontogeny of the obesity of the Zucker and the ‘’cafeteria’’ models. As expected, the ‘’cafeteria’’ rat is more susceptible by feeding related disturbances; this is further evidenced by the interaction of these two peptides involved in feeding regulation: CCK and NPY.