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

Endocrinology. 2007 Jun;148(6):3004-12. doi: 10.1210/en.2007-0016. Epub 2007 Mar 8.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Composition / drug effects*
  • Body Weight / drug effects
  • Cachexia / etiology*
  • Cachexia / pathology*
  • Disease Models, Animal
  • Eating / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Ghrelin
  • Growth Hormone / metabolism
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Neoplasms / complications*
  • Neoplasms / pathology
  • Peptide Hormones / pharmacology*
  • Rats
  • Rats, Inbred F344
  • Tumor Burden / drug effects

Substances

  • Ghrelin
  • Peptide Hormones
  • Insulin-Like Growth Factor I
  • Growth Hormone