Kinzig Kimberly P, Scott Karen A, Hyun Jayson, Bi Sheng, Moran Timothy H
Johns Hopkins School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, MD, USA.
Am J Physiol Regul Integr Comp Physiol. 2006 Jun;290(6):R1565-9. doi: 10.1152/ajpregu.00785.2005. Epub 2006 Jan 19.
The gut peptide ghrelin has been shown to stimulate food intake after both peripheral and central administration, and the hypothalamic arcuate nucleus has been proposed to be the major site for mediating this feeding stimulatory action. Ghrelin receptors are widely distributed in the brain, and hindbrain ghrelin administration has been shown to potently stimulate feeding, suggesting that there may be other sites for ghrelin action. In the present study, we have further assessed potential sites for ghrelin action by comparing the ability of lateral and fourth ventricular ghrelin administration to stimulate food intake and alter patterns of hypothalamic gene expression. Ghrelin (0.32, 1, or 3.2 nmol) in the lateral or fourth ventricle significantly increased food intake in the first 4 h after injection, with no ventricle-dependent differences in degree or time course of hyperphagia. One nanomole of ghrelin into either the lateral or fourth ventricle resulted in similar increases in arcuate nucleus neuropeptide Y mRNA expression. Expression levels of agouti-related peptide or proopiomelanocortin mRNA were not affected by ghrelin administration. These data demonstrate that ghrelin can affect food intake and hypothalamic gene expression through interactions at multiple brain sites.
肠肽胃饥饿素已被证明在经外周和中枢给药后均可刺激食物摄入，并且下丘脑弓状核被认为是介导这种进食刺激作用的主要部位。胃饥饿素受体广泛分布于大脑中，并且已表明在后脑施用胃饥饿素可有效刺激进食，这表明胃饥饿素可能存在其他作用部位。在本研究中，我们通过比较侧脑室和第四脑室注射胃饥饿素刺激食物摄入和改变下丘脑基因表达模式的能力，进一步评估了胃饥饿素的潜在作用部位。侧脑室或第四脑室内注射胃饥饿素（0.32、1或3.2 nmol）在注射后的前4小时显著增加了食物摄入量，在摄食过多的程度或时间进程上没有脑室依赖性差异。向侧脑室或第四脑室内注射1 nmol胃饥饿素会导致弓状核神经肽Y mRNA表达出现类似的增加。刺鼠相关肽或阿黑皮素原mRNA的表达水平不受胃饥饿素给药的影响。这些数据表明，胃饥饿素可通过在多个脑区的相互作用影响食物摄入和下丘脑基因表达。
