Ghrelin Treatment Causes Increased Food Intake and Retention of Lean Body Mass in a Rat Model of Cancer Cachexia

• Published in: Endocrinology (Philadelphia) Vol. 148; no. 6; pp. 3004 - 3012
• Main Authors: DeBoer, Mark D., Zhu, Xin Xia, Levasseur, Peter, Meguid, Michael M., Suzuki, Susumu, Inui, Akio, Taylor, John E., Halem, Heather A., Dong, Jesse Z., Datta, Rakesh, Culler, Michael D., Marks, Daniel L.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.06.2007; Endocrine Society
• Subjects: Animals; Anorexia; Biological and medical sciences; Body Composition - drug effects; Body fat; Body mass; Body Weight - drug effects; Body weight gain; Brain stem; Cachexia; Cachexia - etiology; Cachexia - pathology; Cancer; Disease Models, Animal; Dual energy X-ray absorptiometry; Eating - drug effects; Eating disorders; Food consumption; Food intake; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic - drug effects; Ghrelin; Growth Hormone - metabolism; Hypothalamus; Hypothalamus - drug effects; Hypothalamus - metabolism; Insulin-Like Growth Factor I - metabolism; Interleukin 1 receptors; Lean body mass; Male; Malignancy; Neoplasms - complications; Neoplasms - pathology; Neuropeptide Y; Peptide Hormones - pharmacology; Peptides; Rats; Rats, Inbred F344; Real time; Receptors; Retention; Tumor Burden - drug effects; Tumors; Vertebrates: endocrinology; Weight; Animal model; Rat; Rodentia; Cachexia; Malignant tumor; Feeding; Vertebrata; Mammalia; Treatment; Food intake; Ghrelin; Animal; Lean body mass; Cancer
• ISSN: 0013-7227; 1945-7170; 1945-7170
• DOI: 10.1210/en.2007-0016

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.