Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice.
Leptin is a circulating protein involved in the long-term 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 microg/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.
Barrachina
M D
MD
CURE: Digestive Diseases Research Center, West Los Angeles Veterans Affairs Medical Center, Department of Medicine, and Brain Research Institute, University of California, Los Angeles, CA 90073, USA.
Martínez
V
V
Wang
L
L
Wei
J Y
JY
Taché
Y
Y
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D020109:Devazepide; D004357:Drug Synergism; D005247:Feeding Behavior / Q000187:drug effects*; D005746:Gastric Emptying / Q000187:drug effects; D007150:Immunohistochemistry; D020738:Leptin; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects
D001570:Benzodiazepinones; D020738:Leptin; D011506:Proteins; D002766:Cholecystokinin; D020109:Devazepide; D001839:Bombesin; D002211:Capsaicin