Volkoff Helene, Eykelbosh Angela Joy, Peter Richard Ector
Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
Brain Res. 2003 May 16;972(1-2):90-109. doi: 10.1016/s0006-8993(03)02507-1.
To assess the role of leptin on food intake regulation in goldfish, we examined the effects of central (intracerebroventricular, ICV) and peripheral (intraperitoneal, IP) injections of recombinant murine leptin on feeding behavior. Centrally (100 ng/g) and peripherally (300 ng/g) injected leptin both caused a significant decrease in food intake, compared to the saline-treated controls. To test the hypothesis that leptin influenced orexigenic neuropeptide systems in goldfish, fish were co-injected with neuropeptide Y (NPY) or orexin A and leptin. Both NPY (5 ng/g) and orexin A (10 ng/g) significantly increased food intake. Fish co-injected ICV with NPY (5 ng/g) or orexin A (10 ng/g) and leptin (1 or 10 ng/g) had a food intake lower than that of fish treated with NPY or orexin A alone. NPY mRNA expression in goldfish brain was reduced 2 and 6 h following central injection of leptin. To test the hypothesis that the cholecystokinin (CCK) mediates the effects of leptin in goldfish, fish were simultaneously injected ICV with an ineffective dose of leptin (10 ng/g) and either ICV or IP with an ineffective doses of CCK (1 ng/g ICV or 25 ng/g IP). These fish had a food intake lower than vehicle-treated fish, suggesting that leptin potentiates the satiety actions of CCK. CCK hypothalamic mRNA expression was increased 2 h following central treatment with leptin. The CCK receptor antagonist proglumide blocked both central and peripheral CCK satiety effects. Blockade of CCK brain receptors by proglumide resulted in an inhibition of the leptin-induced decrease in food intake and an attenuation of the inhibiting action of leptin on both NPY- and orexin A-induced feeding. These data suggests that CCK has a role in mediating the effects of leptin on food intake. Fasting potentiated the actions of leptin and attenuated the effects of CCK. Whereas fasting had no effects on the brain mRNA expression of CCK, it increased the brain mRNA expression of NPY and decreased the expression of CART. These changes in neuropeptide expression were partially reversed when fish were treated ICV with leptin. These results provide strong evidence that, in goldfish, leptin influences food intake, in part by modulating the orexigenic effects of NPY and orexin and that its actions are mediated, at least in part, by CCK.
为评估瘦素在金鱼摄食调节中的作用，我们研究了向金鱼脑室内（ICV）和腹腔内（IP）注射重组鼠瘦素对其摄食行为的影响。与注射生理盐水的对照组相比，脑室内注射（100 ng/g）和腹腔内注射（300 ng/g）瘦素均显著降低了金鱼的摄食量。为验证瘦素影响金鱼中促食欲神经肽系统的假说，我们将神经肽Y（NPY）或食欲素A与瘦素共同注射到金鱼体内。NPY（5 ng/g）和食欲素A（10 ng/g）均显著增加了金鱼的摄食量。脑室内将NPY（5 ng/g）或食欲素A（10 ng/g）与瘦素（1或10 ng/g）共同注射的金鱼，其摄食量低于单独注射NPY或食欲素A的金鱼。脑室内注射瘦素后2小时和6小时，金鱼脑中NPY mRNA表达降低。为验证胆囊收缩素（CCK）介导瘦素对金鱼作用的假说，我们将无效剂量的瘦素（10 ng/g）脑室内注射到金鱼体内，同时将无效剂量的CCK（1 ng/g脑室内注射或25 ng/g腹腔内注射）脑室内或腹腔内注射到金鱼体内。这些金鱼的摄食量低于注射溶剂的金鱼，这表明瘦素增强了CCK的饱腹感作用。脑室内注射瘦素后2小时，下丘脑CCK mRNA表达增加。CCK受体拮抗剂丙谷胺可阻断CCK的中枢和外周饱腹感作用。丙谷胺阻断脑中CCK受体后，可抑制瘦素诱导的摄食量减少，并减弱瘦素对NPY和食欲素A诱导摄食的抑制作用。这些数据表明，CCK在介导瘦素对摄食的作用中发挥作用。禁食增强了瘦素的作用，并减弱了CCK的作用。禁食对脑中CCK mRNA表达无影响，但增加了脑中NPY mRNA表达，并降低了可卡因-安非他明调节转录肽（CART）的表达。当脑室内注射瘦素处理金鱼时，这些神经肽表达的变化部分得到逆转。这些结果提供了有力证据，表明在金鱼中，瘦素部分通过调节NPY和食欲素的促食欲作用来影响摄食，且其作用至少部分由CCK介导。
