Ghrelin-induced food intake is mediated via the orexin pathway
Ghrelin-induced food intake is mediated via the orexin pathway
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DOI：
10.1210/en.2002-220788
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发表时间：
2003-04-01
期刊：
影响因子：
4.8
通讯作者：
Nakazato, M
中科院分区：
文献类型：
--
作者：
Toshinai, K;Date, Y;Nakazato, M
下丘脑通过多种神经元和血液来源的信号，将饥饿或饱足的程度与环境状态相结合，调节能量摄入。胃饥饿素是胃和下丘脑产生的一种肽，刺激进食和生长激素的分泌。中央给药的胃饥饿素通过神经肽Y （NPY）和刺痛症相关蛋白系统发挥促氧活性。然而，胃饥饿素和其他下丘脑促氧肽之间的相互作用尚未明确。在这里，我们研究了胃饥饿素和存在于下丘脑外侧的两种产氧肽，即食欲素和黑色素浓缩激素（MCH）之间的解剖相互作用和功能关系。生长素免疫反应性轴突末端与食欲素产生神经元直接突触接触。脑室内给予胃饥饿素可诱导产生食欲素的神经元中Fos（神经元激活的标志）的表达，而在产生mch的神经元中则没有。在抗npy IgG预处理后，Ghrelin仍能诱导食欲素生成神经元中Fos的表达。预处理抗食欲素a IgG和抗食欲素b IgG，但不抗mch IgG，可减弱胃饥饿素诱导的饲养。给药NPY受体拮抗剂进一步减弱抗食欲素- igg治疗大鼠胃饥饿素诱导的摄食。饥饿素诱导的摄食在食欲素敲除小鼠中也受到抑制。本研究发现了一种连接胃饥饿素和食欲素调节摄食行为和能量稳态的下丘脑新途径。
The hypothalamus regulates energy intake by integrating the degree of starvation or satiation with the status of the environment through a variety of neuronal and blood-derived signals. Ghrelin, a peptide produced in the stomach and hypothalamus, stimulates feeding and GH secretion. Centrally administered ghrelin exerts an orexigenic activity through the neuropeptide Y (NPY) and agouti-related protein systems. The interaction between ghrelin and other hypothalamic orexigenic peptides, however, has not been clarified. Here, we investigated the anatomical interactions and functional relationship between ghrelin and two orexigenic peptides, orexin and melanin-concentrating hormone (MCH), present in the lateral hypothalamus. Ghrelin-immunoreactive axonal terminals made direct synaptic contacts with orexin-producing neurons. Intracerebroventricular administration of ghrelin induced Fos expression, a marker of neuronal activation, in orexin-producing neurons but not in MCH-producing neurons. Ghrelin remained competent to induce Fos expression in orexin-producing neurons following pretreatment with anti-NPY IgG. Pretreatment with anti-orexin-A IgG and anti-orexin-B IgG, but not anti-MCH IgG, attenuated ghrelin-induced feeding. Administration of NPY receptor antagonist further attenuated ghrelin-induced feeding in rats treated with anti-orexin-IgGs. Ghrelin-induced feeding was also suppressed in orexin knockout mice. This study identifies a novel hypothalamic pathway that links ghrelin and orexin in the regulation of feeding behavior and energy homeostasis.