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

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.