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Proceedings of the National Academy of Sciences - PNAS, 1997-09, Vol.94 (19), p.10455-10460
1997
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Autor(en) / Beteiligte
Titel
Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice
Ist Teil von
  • Proceedings of the National Academy of Sciences - PNAS, 1997-09, Vol.94 (19), p.10455-10460
Ort / Verlag
United States: National Academy of Sciences of the United States of America
Erscheinungsjahr
1997
Quelle
MEDLINE
Beschreibungen/Notizen
  • Leptin is a circulating protein involved in the long-tern regulation of food intake and body weight. Cholecystokinin (CCK) is released postprandially and elicits satiety signals. We investigated the interaction between leptin and CCK-8 in the short-term regulation of food intake induced by 24-hr fasting in lean mice. Leptin, injected intraperitoneally (i.p.) at low doses (4-120 microgram/kg), which did not influence feeding behavior for the first 3 hr postinjection, decreased food intake dose dependently by 47-83% during the first hour when coinjected with a subthreshold dose of CCK. Such an interaction was not observed between leptin and bombesin. The food-reducing effect of leptin injected with CCK was not associated with alterations in gastric emptying or locomotor behavior. Leptin-CCK action was blocked by systemic capsaicin at a dose inducing functional ablation of sensory afferent fibers and by devazepide, a CCK-A receptor antagonist but not by the CCK-B receptor antagonist, L-365,260. The decrease in food intake which occurs 5 hr after i.p. injection of leptin alone was also blunted by devazepide. Coinjection of leptin and CCK enhanced the number of Fos-positive cells in the hypothalamic paraventricular nucleus by 60% whereas leptin or CCK alone did not modify Fos expression. These results indicate the existence of a functional synergistic interaction between leptin and CCK leading to early suppression of food intake which involves CCK-A receptors and capsaicin-sensitive afferent fibers

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