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Ghrelin treatment causes increased food intake and retention of lean body mass in a rat model of cancer cachexia.

Abstract
Cancer cachexia is a debilitating syndrome of anorexia and loss of lean body mass that accompanies many malignancies. Ghrelin is an orexigenic hormone with a short half-life that has been shown to improve food intake and weight gain in human and animal subjects with cancer cachexia. We used a rat model of cancer cachexia and administered human ghrelin and a synthetic ghrelin analog BIM-28131 via continuous infusion using sc osmotic minipumps. Tumor-implanted rats receiving human ghrelin or BIM-28131 exhibited a significant increase in food consumption and weight gain vs. saline-treated animals. We used dual-energy x-ray absorptiometry scans to show that the increased weight was due to maintenance of lean mass vs. a loss of lean mass in saline-treated animals. Also, BIM-28131 significantly limited the loss of fat mass normally observed in tumor-implanted rats. We further performed real-time PCR analysis of the hypothalami and brainstems and found that ghrelin-treated animals exhibited a significant increase in expression of orexigenic peptides agouti-related peptide and neuropeptide Y in the hypothalamus and a significant decrease in the expression of IL-1 receptor-I transcript in the hypothalamus and brainstem. We conclude that ghrelin and a synthetic ghrelin receptor agonist improve weight gain and lean body mass retention via effects involving orexigenic neuropeptides and antiinflammatory changes.
AuthorsMark D DeBoer, Xin Xia Zhu, Peter Levasseur, Michael M Meguid, Susumu Suzuki, Akio Inui, John E Taylor, Heather A Halem, Jesse Z Dong, Rakesh Datta, Michael D Culler, Daniel L Marks
JournalEndocrinology (Endocrinology) Vol. 148 Issue 6 Pg. 3004-12 (Jun 2007) ISSN: 0013-7227 [Print] United States
PMID17347304 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Ghrelin
  • Peptide Hormones
  • Insulin-Like Growth Factor I
  • Growth Hormone
Topics
  • Animals
  • Body Composition (drug effects)
  • Body Weight (drug effects)
  • Cachexia (etiology, pathology)
  • Disease Models, Animal
  • Eating (drug effects)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Ghrelin
  • Growth Hormone (metabolism)
  • Hypothalamus (drug effects, metabolism)
  • Insulin-Like Growth Factor I (metabolism)
  • Male
  • Neoplasms (complications, pathology)
  • Peptide Hormones (pharmacology)
  • Rats
  • Rats, Inbred F344
  • Tumor Burden (drug effects)

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