Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice
Synergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice
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DOI：
10.1073/pnas.94.19.10455
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发表时间：
1997-09-16
影响因子：
11.1
通讯作者：
Tache, Y
中科院分区：
文献类型：
--
作者：
Barrachina, MD;Martinez, V;Tache, Y
瘦素是一种循环蛋白，参与食物摄入和体重的长期调节。胆囊收缩素（CCK）是餐后释放的兴奋性饱足信号。我们研究了瘦素和CCK-8之间的相互作用，在短期调节的食物摄入量诱导的24小时禁食瘦小鼠。瘦素，腹膜内注射（i. p.）在低剂量（4-120 μ g/kg）下，当与阈下剂量的CCK共注射时，在注射后的第一个3小时内不影响摄食行为，在第一个小时内摄食量依赖性地减少47-83%。在瘦素和蛙皮素之间没有观察到这种相互作用。瘦素注射CCK的减食作用与胃排空或运动行为的改变无关。全身性辣椒素在诱导感觉传入纤维功能性消融的剂量下阻断Leptin-CCK作用，并且阻断CCK-A受体拮抗剂devazepide，但不阻断CCK-B受体拮抗剂L-365，260。在腹膜内注射单独的瘦素后5小时发生的食物摄入的减少也被devazepide减弱。共注射瘦素和CCK增强了60%的下丘脑室旁核的Fos阳性细胞的数量，而单独的瘦素或CCK没有修改Fos的表达。这些结果表明瘦素和CCK之间存在功能性协同作用，导致食物摄入的早期抑制，这涉及CCK-A受体和辣椒素敏感的传入纤维。
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 mu g/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.