Des-Acyl Ghrelin Directly Targets the Arcuate Nucleus in a Ghrelin-Receptor Independent Manner and Impairs the Orexigenic Effect of Ghrelin
Des-Acyl Ghrelin Directly Targets the Arcuate Nucleus in a Ghrelin-Receptor Independent Manner and Impairs the Orexigenic Effect of Ghrelin
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DOI：
10.1111/jne.12349
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发表时间：
2016-02-01
影响因子：
3.2
通讯作者：
Perello, M.
中科院分区：
文献类型：
--
作者：
Fernandez, G.;Cabral, A.;Perello, M.
Ghrelin是一种胃源性辛酰化肽激素，通过其特异性受体生长激素促分泌素受体（GHSR）发挥多种公认的生物学作用。在血浆中，还存在一种去辛酰化形式的生长素释放肽，称为去酰基生长素释放肽（DAG）。DAG被认为是一种信号分子，具有特定的靶点，包括大脑，并调节一些生理功能。然而，迄今为止还没有报道DAG的特异性受体，因此，DAG作为激素的潜在作用仍然是一个争论的问题。在本研究中，我们表明，DAG特异性结合并作用于弓状核（ARC）细胞的一个子集，在GHSR独立的方式。由DAG荧光示踪剂标记的ARC细胞包括神经肽Y（NPY）和非NPY神经元。鉴于ARC在食欲调节中的作用已得到证实，我们测试了集中施用DAG对食物摄入的影响。我们发现，DAG没有影响黑暗阶段的喂养，以及食物的摄入量，饥饿期后，然而，它损害了食欲的外周管理ghrelin的行动。因此，我们得出结论，DAG直接针对ARC神经元和拮抗食欲的外周给药的胃饥饿素的影响。
Ghrelin is a stomach-derived octanoylated peptide hormone that plays a variety of well-established biological roles acting via its specific receptor known as growth hormone secretagogue receptor (GHSR). In plasma, a des-octanoylated form of ghrelin, named des-acyl ghrelin (DAG), also exists. DAG is suggested to be a signalling molecule that has specific targets, including the brain, and regulates some physiological functions. However, no specific receptor for DAG has been reported until now, and, consequently, the potential role of DAG as a hormone has remained a matter of debate. In the present study, we show that DAG specifically binds to and acts on a subset of arcuate nucleus (ARC) cells in a GHSR-independent manner. ARC cells labelled by a DAG fluorescent tracer include the neuropeptide Y (NPY) and non-NPY neurones. Given the well-established role of the ARC in appetite regulation, we tested the effect of centrally administered DAG on food intake. We found that DAG failed to affect dark phase feeding, as well as food intake, after a starvation period; however, it impaired the orexigenic actions of peripherally administered ghrelin. Thus, we conclude that DAG directly targets ARC neurones and antagonises the orexigenic effects of peripherally administered ghrelin.