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.
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Authors | Mark 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 |
Journal | Endocrinology
(Endocrinology)
Vol. 148
Issue 6
Pg. 3004-12
(Jun 2007)
ISSN: 0013-7227 [Print] United States |
PMID | 17347304
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ghrelin
- Peptide Hormones
- Insulin-Like Growth Factor I
- Growth Hormone
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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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