Leptin deficiency induced by fasting impairs the satiety response to cholecystokinin.
Leptin administration potentiates the satiety response to signals such as cholecystokinin (CCK), that are released from the gut during a meal. To investigate the physiological relevance of this observation, we hypothesized that leptin deficiency, induced by fasting, attenuates the satiety response to CCK. To test this hypothesis, 48-h-fasted or fed rats were injected with i.p. saline or CCK. Fasting blunted the satiety response to 3.0 microg/kg CCK, such that 30-min food intake was suppressed by 65.1% (relative to saline-treated controls) in fasted rats vs. 85.9% in the fed state (P < 0.05). In a subsequent experiment, rats were divided into three groups: 1) vehicle/fed; 2) vehicle/fasted; and 3) leptin-replaced/fasted; and each group received 3.0 microg/kg i.p. CCK. As expected, the satiety response to CCK was attenuated by 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 prevented by leptin replacement (0.7 +/- 0.2 g, P < 0.05 vs. vehicle/fasted; P = not significant vs. vehicle/fed). To investigate whether elevated neuropeptide Y (NPY) signaling plays a role in the effect of leptin deficiency to impair the response to CCK, we measured the response to 3.0 microg/kg i.p. CCK after treatment with 7.5 microg intracerebroventricular NPY. We found that both CCK-induced satiety and its ability to increase c-Fos-like-immunoreactivity in key brainstem-feeding centers were attenuated by NPY pretreatment. We conclude that an attenuated response to meal-related satiety signals is triggered by leptin deficiency and may contribute to increased food intake.
McMinn
J E
JE
Program in Nutritional Sciences, University of Washington, Seattle 98195, USA.
Sindelar
D K
DK
Havel
P J
PJ
Schwartz
M W
MW
D000818:Animals; D001923:Brain Chemistry; D002766:Cholecystokinin / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D005215:Fasting / Q000502:physiology*; D007276:Injections, Intraventricular; D020738:Leptin / Q000172:deficiency*; D008297:Male; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012527:Satiation / Q000187:drug effects*
D020738:Leptin; D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D002766:Cholecystokinin