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.
DeBoer
Mark D
MD
Center for the Study of Weight Regulation, Oregon Health and Science University, 707 SW Gaines Road, Portland, OR 97239, USA.
Zhu
Xin Xia
XX
Levasseur
Peter
P
Meguid
Michael M
MM
Suzuki
Susumu
S
Inui
Akio
A
Taylor
John E
JE
Halem
Heather A
HA
Dong
Jesse Z
JZ
Datta
Rakesh
R
Culler
Michael D
MD
Marks
Daniel L
DL
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
D054439:Ghrelin; D036361:Peptide Hormones; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone