Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and agouti-related protein mRNA levels and body weight in rats
Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and agouti-related protein mRNA levels and body weight in rats
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DOI：
10.2337/diabetes.50.11.2438
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发表时间：
2001-11-01
期刊：
影响因子：
7.7
通讯作者：
Wakabayashi, I
中科院分区：
文献类型：
--
作者：
Kamegai, J;Tamura, H;Wakabayashi, I
Ghrelin是生长激素促分泌素受体（GHS-R）的内源性配体，最初从大鼠胃中纯化。与合成的生长激素促分泌素（GHS）一样，生长激素释放肽在静脉给药后特异性地释放生长激素（GH）。还一致的GHS的中枢作用，ghrelin免疫反应细胞被证明是位于下丘脑弓状核以及胃。最近，我们发现，一个单一的中央管理ghrelin增加食物摄入量和下丘脑刺豚鼠相关蛋白（AGRP）基因表达的啮齿动物，和食欲的影响，这种肽似乎是独立的GH释放活性。然而，长期输注ghrelin对摄食量和体重的影响及其可能的机制尚未阐明。在这项研究中，我们确定了慢性脑室内治疗与生长激素释放肽对代谢因子和神经肽基因的影响，这些基因在下丘脑神经元中表达，这些神经元先前已被证明表达GHS-R并调节食物消耗。慢性中枢给药大鼠生长素释放肽（1 μ g/大鼠每12小时，持续72小时）显着增加食物摄入量和体重。然而，它不影响血浆胰岛素，葡萄糖，瘦素，或GH浓度。我们还发现，长期中枢给予ghrelin可增加弓状核神经肽Y（NPY）mRNA水平（生理盐水处理对照组的151.0 +/- 10.1%; P < 0.05）和AGRP mRNA水平（生理盐水处理对照组的160.0 +/- 22.5%; P < 0.05）。因此，ghrelin的主要下丘脑靶点是含有NPY/AGRP的神经元，ghrelin是脑和胃中新发现的食欲肽。
Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), was originally purified from the rat stomach. Like the synthetic growth hormone secretagogues (GHSs), ghrelin specifically releases growth hormone (GH) after intravenous administration. Also consistent with the central actions of GHSs, ghrelin-immunoreactive cells were shown to be located in the hypothalamic arcuate nucleus as well as the stomach. Recently, we showed that a single central administration of ghrelin increased food intake and hypothalamic agouti-related protein (AGRP) gene expression in rodents, and the orexigenic effect of this peptide seems to be independent of its GH-releasing activity. However, the effect of chronic infusion of ghrelin on food consumption and body weight and their possible mechanisms have not been elucidated. In this study, we determined the effects of chronic intracerebroventricular treatment with ghrelin on metabolic factors and on neuropeptide genes that are expressed in hypothalamic neurons that have been previously shown to express the GHS-R and to regulate food consumption. Chronic central administration of rat ghrelin (1 mug/rat every 12 h for 72 h) significantly increased food intake and body weight. However, it did not affect plasma insulin, glucose, leptin, or GH concentrations. We also found that chronic central administration of ghrelin increased both neuropeptide Y (NPY) mRNA levels (151.0 +/- 10.1% of saline-treated controls; P < 0.05) and AGRP mRNA levels (160.0 +/- 22.5% of saline-treated controls; P < 0.05) in the arcuate nucleus. Thus, the primary hypothalamic targets of ghrelin are NPY/AGRP-containing neurons, and ghrelin is a newly discovered orexigenic peptide in the brain and stomach.