Leptin deficiency induced by fasting impairs the satiety response to cholecystokinin

Leptin administration potentiates the satiety response to signals such as c holecystokinin (CCK), that are released from the gut during a meat To inves tigate the physiological relevance of this observation, we hypothesized tha t leptin deficiency, induced by fasting, attenuates the satiety response to CCK. To test this hypothesis, 48-h-fasted or fed rats mere injected with i p saline or CCK. Fasting blunted the satiety response to 3.0 mug/kg CCB suc h that 30-min food intake was suppressed by 65.1% (relative to saline-treat ed controls) in fasted rats vs. 85.9% in the fed state (P < 0.05). In a sub sequent experiment, rats were divided into three groups: 1) vehicle/fed; 2) vehicle/fasted; and 3) leptin-replaced/fasted; and each group received 3.0 <mu>g/kg ip CCK. As expected, the satiety response to CCK was attenuated b y fasting in vehicle-treated rats (30-min food intake: vehicle/fed, 0.3 +/- 0.1 g; vehicle/fasted, 1.7 +/- 0.4 g; P < 0.01), and this effect was preve nted by leptin replacement(0.7 +/- 0.2 g, P < 0.05 vs, vehicle/fasted; P = not significant vs. vehicle/fed). To investigate whether elevated neuropept ide Y (NPY) signaling plays a role in the effect of leptin deficiency to im pair the response to CCK, we measured the response to 3.0 mug/kg ip CCK aft er treatment with 7.5 mug intracerebroventricular NPY. We found that both C CK-induced satiety and its ability to increase c-Fos-like-immunoreactivity in key brainstem-feeding centers were attenuated by NPY pretreatment. We co nclude that an attenuated response to meal-related satiety signals is trigg ered by leptin deficiency and may contribute to increased food intake.