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金鱼中“肠-脑”激素胃饥饿素与昼夜节律系统之间的相互作用。对生物钟基因表达和食物预期活动的影响。

Crosstalking between the "gut-brain" hormone ghrelin and the circadian system in the goldfish. Effects on clock gene expression and food anticipatory activity.

作者信息

Nisembaum Laura G, de Pedro Nuria, Delgado María J, Isorna Esther

机构信息

Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, 28040 Madrid, Spain.

Departamento de Fisiología (Fisiología Animal II), Facultad de Biología, Universidad Complutense de Madrid, 28040 Madrid, Spain.

出版信息

Gen Comp Endocrinol. 2014 Sep 1;205:287-95. doi: 10.1016/j.ygcen.2014.03.016. Epub 2014 Mar 27.

DOI:10.1016/j.ygcen.2014.03.016
PMID:24681192
Abstract

Ghrelin is a potent orexigenic signal mainly synthesized in the stomach and foregut of vertebrates. Recent studies in rodents point out that ghrelin could also act as an input for the circadian system and/or as an output of peripheral food-entrainable oscillators, being involved in the food anticipatory activity (FAA). In this study we pursue the possible interaction of ghrelin with the circadian system in a teleost, the goldfish (Carassius auratus). First, we analyzed if ghrelin is able to modulate the core clock functioning by regulating clock gene expression in fish under a light/dark cycle 12L:12D and fed at 10 am. As expected the acute intraperitoneal (IP) injection of goldfish ghrelin (gGRL[1-19], 44 pmol/g bw) induced the expression of hypothalamic orexin. Moreover, ghrelin also induced (∼ 2-fold) some Per clock genes in hypothalamus and liver. This effect was partially counteracted in liver by the ghrelin antagonist ([D-Lys(3)]-GHRP-6, 100 pmol/g bw). Second, we investigated if ghrelin is involved in daily FAA rhythms. With this aim locomotor activity was studied in response to IP injections (5-10 days) of gGRL[1-19] and [D-Lys(3)]-GHRP-6 at the doses above indicated. Ghrelin and saline injected fish showed similar 24h activity patterns. However, ghrelin antagonist treatment abolished the FAA in schedule fed fish under 24h light, suggesting the involvement of the endogenous ghrelin system in this pre-feeding activity. Altogether these results suggest that ghrelin could be acting as an input for the entrainment of the food-entrainable oscillators in the circadian organization of goldfish.

摘要

胃饥饿素是一种主要在脊椎动物的胃和前肠合成的强效促食欲信号。近期对啮齿动物的研究指出,胃饥饿素还可能作为昼夜节律系统的一个输入信号和/或作为外周食物可调节振荡器的一个输出信号,参与食物预期活动(FAA)。在本研究中,我们探究了胃饥饿素与硬骨鱼金鱼(Carassius auratus)的昼夜节律系统之间可能存在的相互作用。首先,我们分析了在12小时光照:12小时黑暗周期且上午10点喂食的条件下,胃饥饿素是否能够通过调节鱼类时钟基因的表达来调控核心时钟功能。正如预期的那样,腹腔注射金鱼胃饥饿素(gGRL[1-19],44 pmol/g体重)可诱导下丘脑食欲素的表达。此外,胃饥饿素还能诱导下丘脑和肝脏中一些Per时钟基因(约2倍)的表达。胃饥饿素拮抗剂([D-Lys(3)]-GHRP-6,100 pmol/g体重)可部分抵消肝脏中的这种效应。其次,我们研究了胃饥饿素是否参与每日的食物预期活动节律。为此,我们针对上述剂量的gGRL[1-19]和[D-Lys(3)]-GHRP-6进行腹腔注射(5 - 10天),并研究其对运动活动的影响。注射胃饥饿素和生理盐水的鱼表现出相似的24小时活动模式。然而,胃饥饿素拮抗剂处理消除了在24小时光照条件下定时喂食的鱼的食物预期活动,这表明内源性胃饥饿素系统参与了这种进食前活动。总之,这些结果表明胃饥饿素可能作为一种输入信号,参与金鱼昼夜节律组织中食物可调节振荡器的同步化过程。

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