Leptin deficiency induced by fasting impairs the satiety response to cholecystokinin

Julie E. McMinn, Dana K. Sindelar, Peter J Havel, Michael W. Schwartz

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

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 ip saline or CCK. Fasting blunted the satiety response to 3.0 μg/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 μg/kg ip 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 μg/kg ip CCK after treatment with 7.5 μg 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.

Original languageEnglish (US)
Pages (from-to)4442-4448
Number of pages7
JournalEndocrinology
Volume141
Issue number12
DOIs
StatePublished - 2000

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Satiety Response
Cholecystokinin
Leptin
Fasting
Neuropeptide Y
Eating
Meals
Aptitude
Brain Stem

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Leptin deficiency induced by fasting impairs the satiety response to cholecystokinin. / McMinn, Julie E.; Sindelar, Dana K.; Havel, Peter J; Schwartz, Michael W.

In: Endocrinology, Vol. 141, No. 12, 2000, p. 4442-4448.

Research output: Contribution to journalArticle

McMinn, Julie E. ; Sindelar, Dana K. ; Havel, Peter J ; Schwartz, Michael W. / Leptin deficiency induced by fasting impairs the satiety response to cholecystokinin. In: Endocrinology. 2000 ; Vol. 141, No. 12. pp. 4442-4448.
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