title: 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.
authors.affiliation: Center for the Study of Weight Regulation, Oregon Health and Science University, 707 SW Gaines Road, Portland, OR 97239, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: DeBoer
authors.forename: Xin Xia
authors.initials: XX
authors.lastname: Zhu
authors.forename: Peter
authors.initials: P
authors.lastname: Levasseur
authors.forename: Michael M
authors.initials: MM
authors.lastname: Meguid
authors.forename: Susumu
authors.initials: S
authors.lastname: Suzuki
authors.forename: Akio
authors.initials: A
authors.lastname: Inui
authors.forename: John E
authors.initials: JE
authors.lastname: Taylor
authors.forename: Heather A
authors.initials: HA
authors.lastname: Halem
authors.forename: Jesse Z
authors.initials: JZ
authors.lastname: Dong
authors.forename: Rakesh
authors.initials: R
authors.lastname: Datta
authors.forename: Michael D
authors.initials: MD
authors.lastname: Culler
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Marks
mesh_terms: D000818:Animals; D001823:Body Composition / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000209:etiology* / Q000473:pathology*; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009369:Neoplasms / Q000150:complications* / Q000473:pathology; D036361:Peptide Hormones / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D054439:Ghrelin; D036361:Peptide Hormones; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone