Stevanović D, Nesić D, Milosević V, Starcević V, Severs W B
Institute of Medical Physiology, University of Belgrade, School of Medicine, Visegradska 26/II, Belgrade 11001, Serbia.
Regul Pept. 2008 Apr 10;147(1-3):52-9. doi: 10.1016/j.regpep.2008.01.003. Epub 2008 Jan 16.
Ghrelin, an endogenous ligand for the growth-hormone-secretagogue receptor, is a 28-amino acid peptide with a post-translational acyl modification necessary for its activity. It has central nervous system actions that affect appetite, body mass and energy balance. An intracerebroventricular (ICV) injection protocol of sub-nanomolar doses of ghrelin, known to alter the morphology of ACTH and GH producing pituicytes and plasma levels of these hormones, was used to provide an overview of metabolic changes linked to energy metabolism. Variables measured were: food intake (FI), water intake (WI), fecal mass, urine volume, body weight (BW), retroperitoneal (RP) and epididymal (EPI) white adipose tissue (WAT), and changes in serum leptin, insulin, triglycerides, cholesterol, and glucose. Five injections of rat ghrelin or PBS (n=8 per group) were given ICV every 24 h (1 microg/5 muL PBS) to adult male rats. Ghrelin had a positive and cumulative effect on FI, WI and BW (p<0.05), but not feces mass or urine volume (p>0.05). Centrally applied ghrelin clearly increased RP WAT (by 235%, p<0.001), EPI WAT (by 85%, p<0.05) and serum insulin levels (by 43%, p<0.05), and decreased serum leptin levels (by 77%, p<0.05) without (p>0.05) evoking changes in blood triglyceride cholesterol, or glucose levels. These data and the available literature clearly document that exposure of the brain of normal rats, over time, to sub-nanomolar doses of ghrelin results in metabolic dysregulation culminating in increased body mass, consummatory behavior, and lipid stores as well as changes in blood leptin/insulin levels. Thus, modulation of central ghrelin receptors may represent a pharmacological approach for controlling multiple factors involved in energy balance and obesity.
胃饥饿素是生长激素促分泌素受体的内源性配体，是一种由28个氨基酸组成的肽，其活性需要翻译后酰基修饰。它具有影响食欲、体重和能量平衡的中枢神经系统作用。已知亚纳摩尔剂量的胃饥饿素进行脑室内（ICV）注射可改变促肾上腺皮质激素（ACTH）和生长激素（GH）分泌细胞的形态以及这些激素的血浆水平，本研究采用该注射方案概述与能量代谢相关的代谢变化。所测量的变量包括：食物摄入量（FI）、饮水量（WI）、粪便质量、尿量、体重（BW）、腹膜后（RP）和附睾（EPI）白色脂肪组织（WAT），以及血清瘦素、胰岛素、甘油三酯、胆固醇和葡萄糖的变化。每24小时给成年雄性大鼠进行5次脑室内注射大鼠胃饥饿素或磷酸盐缓冲盐水（PBS）（每组n = 8）（1微克/5微升PBS）。胃饥饿素对食物摄入量、饮水量和体重有积极的累积效应（p<0.05），但对粪便质量或尿量无影响（p>0.05）。脑内应用胃饥饿素明显增加了腹膜后白色脂肪组织（增加235%，p<0.001）、附睾白色脂肪组织（增加85%，p<0.05）和血清胰岛素水平（增加43%，p<0.05），并降低了血清瘦素水平（降低77%，p<0.05），而未引起血液甘油三酯、胆固醇或葡萄糖水平的变化（p>0.05）。这些数据和现有文献清楚地表明，正常大鼠的大脑长期暴露于亚纳摩尔剂量的胃饥饿素会导致代谢失调，最终导致体重增加、摄食行为和脂质储存增加，以及血液瘦素/胰岛素水平的变化。因此，调节中枢胃饥饿素受体可能是一种控制能量平衡和肥胖相关多种因素的药理学方法。
