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1 Department of Medicine, Division of Hepatology, Gastroenterology, and Endocrinology, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Germany
2 NOXXON Pharma AG, Berlin, Germany
3 Department of Medicine, Division of Psychosomatic Medicine and Psychotherapy, Charité, Campus Charité Mitte, Universitätsmedizin Berlin, Germany
4 Department of Medicine, Division of Hepatology, Gastroenterology, and Endocrinology, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Germany, and Department of Medicine, Division of Psychosomatic Medicine and Psychotherapy, Charité, Campus Charité Mitte, Universitätsmedizin Berlin, Germany
Correspondence to:
Correspondence to:
Dr H Mönnikes
Department of Medicine, Division of Hepatology, Gastroenterology, and Endocrinology, Charité-School of Medicine, Campus Virchow-Klinikum, Medical Faculty of Freie Universität and Humboldt-Universität at Berlin, Augustenburger Platz 1, 13353 Berlin, Germany; hubert.moennikes{at}charite.de
Background and aims: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Abbreviations: GHS-R1a, growth hormone secretagogue receptor 1a; ARC, arcuate nucleus; SELEX, systematic evolution of ligands by exponential enrichment; PBS, phosphate buffered saline; c-FLI, c-Fos-like immunoreactivity
Keywords: ghrelin; obesity; antagonism; NOX-B11; food intake; rat
Relevant Article
Gut 2006 55: 754-755.
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