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在C57BL/6小鼠中,连续10天慢性中枢给予apelin-13会增加食物摄入量、体重、运动活动和体温。

Chronic central administration of apelin-13 over 10 days increases food intake, body weight, locomotor activity and body temperature in C57BL/6 mice.

作者信息

Valle A, Hoggard N, Adams A C, Roca P, Speakman J R

机构信息

Grup de Metabolisme Energètic i Nutrició, Departament de Biologia Fonamental i Ciències de la Salut, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, Palma de Mallorca, Spain.

出版信息

J Neuroendocrinol. 2008 Jan;20(1):79-84. doi: 10.1111/j.1365-2826.2007.01617.x.

Abstract

The peptide apelin has been located in a wide range of tissues, including the gastrointestinal tract, stomach and adipose tissue. Apelin and its receptor has also been detected in the arcuate and paraventricular nuclei of the hypothalamus, which are involved in the control of feeding behaviour and energy expenditure. This distribution suggests apelin may play a role in energy homeostasis, but previous attempts to discern the effects of apelin by acute injection into the brain have yielded conflicting results. We examined the effect of a chronic 10-day intracerebroventricular (i.c.v.) infusion of apelin-13 into the third ventricle on food intake, body temperature and locomotor activity in C57BL/6 mice. Apelin-13 (1 microg/day) increased food intake significantly on days 3-7 of infusion; thereafter, food intake of treated and control individuals converged. This convergence was potentially because of progressive conversion of apelin-13 to [Pyr(1)]apelin-13 which has a four-fold lower receptor binding affinity at the orphan G protein-coupled receptor, APJ. Locomotor activity was also higher in the apelin-treated mice, especially during the nocturnal peak, when most feeding occurs, and the first hours of the light phase. Body temperature was also elevated during this increased period of activity, but was otherwise unaffected. Apelin-13-infused animals gained more weight than the saline-infused controls, suggesting the elevated locomotor activity did not offset the increased food intake. Elevated locomotion and the consequent increases in body temperature were probably secondary effects to the increased food intake. These results suggest that apelin-13 may play a central role in the control of feeding behaviour and is one of only two peripheral ligands known to stimulate rather than inhibit intake. As apelin production is elevated during obesity, this may provide an important feed-forward mechanism exacerbating the problem. Antagonists of the apelin receptor may therefore be useful pharmaceuticals in the treatment of obesity.

摘要

肽apelin存在于多种组织中,包括胃肠道、胃和脂肪组织。在下丘脑的弓状核和室旁核中也检测到了apelin及其受体,这些核参与进食行为和能量消耗的控制。这种分布表明apelin可能在能量稳态中发挥作用,但之前通过急性脑内注射来辨别apelin作用的尝试产生了相互矛盾的结果。我们研究了向C57BL/6小鼠第三脑室慢性脑室内(i.c.v.)输注apelin-13 10天对食物摄入、体温和运动活动的影响。在输注的第3至7天,apelin-13(1微克/天)显著增加了食物摄入量;此后,治疗组和对照组的食物摄入量趋于一致。这种趋同可能是由于apelin-13逐渐转化为[Pyr(1)]apelin-13,后者在孤儿G蛋白偶联受体APJ上的受体结合亲和力低四倍。在接受apelin治疗的小鼠中,运动活动也更高,尤其是在夜间高峰(此时大多数进食发生)以及光照期的最初几个小时。在活动增加期间体温也升高,但在其他方面没有受到影响。输注apelin-13的动物比输注生理盐水的对照组体重增加更多,这表明运动活动的增加并没有抵消食物摄入量的增加。运动增加以及随之而来的体温升高可能是食物摄入量增加的继发效应。这些结果表明,apelin-13可能在进食行为的控制中起核心作用,并且是已知的仅有的两种刺激而非抑制摄入量的外周配体之一。由于肥胖期间apelin的产生会增加,这可能提供了一个加剧问题的重要前馈机制。因此,apelin受体拮抗剂可能是治疗肥胖症的有用药物。

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