Desacyl ghrelin inhibits the orexigenic effect of peripherally injected ghrelin in rats

被引:160
作者
Inhoff, Tobias [2 ]
Moennikes, Hubert [5 ,6 ]
Noetzel, Steffen [2 ]
Stengel, Andreas [3 ,4 ]
Goebel, Miriam [3 ,4 ]
Dinh, Q. Thai [1 ]
Riedl, Andrea [1 ]
Bannert, Norbert [7 ]
Wisser, Anna-Sophia [2 ]
Wiedenmann, Bertram [2 ]
Klapp, Burghard F. [1 ]
Tache, Yvette [4 ]
Kobelt, Peter [1 ,2 ]
机构
[1] Charite, Div Psychosomat Med & Psychotherapy, Dept Med, D-10117 Berlin, Germany
[2] Charite, Div Hepatol Gastroenterol & Endocrinol, Dept Med, D-10117 Berlin, Germany
[3] Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress,Digest Dis Div, Los Angeles, CA 90024 USA
[4] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA
[5] Martin Luther Hosp, Dept Med, Berlin, Germany
[6] Martin Luther Hosp, Inst Neurogastroenterol, Berlin, Germany
[7] Robert Koch Inst, D-1000 Berlin, Germany
关键词
Rat; Desacyl ghrelin; Ghrelin; Food intake; c-Fos; ARC;
D O I
10.1016/j.peptides.2008.09.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Studies showed that the metabolic unlike the neuroendocrine effects of ghrelin could be abrogated by co-administered unacylated ghrelin. The aim was to investigate the interaction between ghrelin and desacyl ghrelin administered intraperitoneally on food intake and neuronal activity (c-Fos) in the arcuate nucleus in non-fasted rats. Ghrelin (13 mu g/kg) significantly increased food intake within the first 30 min post-injection. Desacyl ghrelin at 64 and 127 mu g/kg injected simultaneously with ghrelin abolished the stimulatory effect of ghrelin on food intake. Desacyl ghrelin alone at both doses did not alter food intake. Both doses of desacyl ghrelin injected separately in the light phase had no effects on food intake when rats were fasted for 12 h. Ghrelin and desacyl ghrelin (64 mu g/kg) injected alone increased the number of Fos positive neurons in the arcuate nucleus compared to vehicle. The effect on neuronal activity induced by ghrelin was significantly reduced when injected simultaneously with desacyl ghrelin. Double labeling revealed that nesfatin-1 immunoreactive neurons in the arcuate nucleus are activated by simultaneous injection of ghrelin and desacyl ghrelin. These results suggest that desacyl ghrelin suppresses ghrelin-induced food intake by curbing ghrelin-induced increased neuronal activity in the arcuate nucleus and recruiting nesfatin-1 immunopositive neurons. (c) 2008 Elsevier Inc. All rights reserved.
引用
收藏
页码:2159 / 2168
页数:10
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