产矿性
生长素
内科学
内分泌学
弓状核
生长激素促分泌素受体
化学
氮氧化物
受体
下丘脑
食欲
医学
神经肽
神经肽Y受体
有机化学
燃烧
作者
Peter Kobelt,Steffen Helmling,Andreas Stengel,Britta Wlotzka,Viola Andresen,B. F. Klapp,Bertram Wiedenmann,Sven Klussmann,Hubert Mönnikes
出处
期刊:Gut
[BMJ]
日期:2006-06-01
卷期号:55 (6): 788-792
被引量:62
标识
DOI:10.1136/gut.2004.061010
摘要
Ghrelin, the natural ligand of the growth hormone secretagogue receptor 1a, is the most powerful peripherally active orexigenic agent known. In rodents, ghrelin administration stimulates growth hormone release, food intake, and adiposity. Because of these effects, blocking of ghrelin has been widely discussed as a potential treatment for obesity. Spiegelmer NOX-B11 is a synthetic l-oligonucleotide, which was previously shown to bind ghrelin. We examined the effects of NOX-B11 on ghrelin induced neuronal activation and food intake in non-fasted rats.Animals received various doses of NOX-B11, inactive control Spiegelmer, or vehicle intravenously. Ghrelin or vehicle was administered intraperitoneally 12 hours later and food intake was measured over four hours. Neuronal activation was assessed as c-Fos-like immunoreactivity in the arcuate nucleus.Treatment with NOX-B11 30 nmol suppressed ghrelin induced c-Fos-like immunoreactivity in the arcuate nucleus and blocked the ghrelin induced increase in food intake within the first half hour after ghrelin injection (mean 1.13 (SEM 0.59) g/kg body weight; 4.94 (0.63) g/kg body weight versus 0.58 (0.58) g/kg body weight; p<0.0001). Treatment with NOX-B11 1 nmol or control Spiegelmer had no effect whereas treatment with NOX-B11 10 nmol showed an intermediate effect on ghrelin induced food intake.Spiegelmer NOX-B11 suppresses ghrelin induced food intake and c-Fos induction in the arcuate nucleus in rats. The use of an anti-ghrelin Spiegelmer could be an innovative new approach to inhibit the biological action of circulating ghrelin. This may be of particular relevance to conditions associated with elevated plasma ghrelin, such as the Prader-Willi syndrome.
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