Article Text

PDF
Anti-ghrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats
  1. P Kobelt1,*,
  2. S Helmling2,*,
  3. A Stengel1,
  4. B Wlotzka2,
  5. V Andresen3,
  6. B F Klapp3,
  7. B Wiedenmann1,
  8. S Klussmann2,
  9. H Mönnikes4
  1. 1Department of Medicine, Division of Hepatology, Gastroenterology, and Endocrinology, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, Germany
  2. 2NOXXON Pharma AG, Berlin, Germany
  3. 3Department of Medicine, Division of Psychosomatic Medicine and Psychotherapy, Charité, Campus Charité Mitte, Universitätsmedizin Berlin, Germany
  4. 4Department 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
  1. 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

Abstract

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.

  • 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
  • ghrelin
  • obesity
  • antagonism
  • NOX-B11
  • food intake
  • rat

Statistics from Altmetric.com

Footnotes

  • Published online first 30 June 2005

  • * P Kobelt and S Helmling authors contributed equally to this work.

  • Conflict of interest: None declared.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles