Continuous intravenous infusion of ghrelin does not stimulate feeding in tumor-bearing rats.
The development of anorexia continues to be a serious treatment issue for cancer patients. Because the orexigenic peptide, ghrelin, is active through systemic routes and activates hypothalamic neuropeptide systems known to be refractory in anorectic tumor-bearing (TB) rats, we investigated whether it would prevent the development of cancer anorexia when infused continuously intravenously. The 24-h food intake was increased in nontumor-bearing (NTB) rats at a dose of 288 microg/day ghrelin. However, no tested dose of ghrelin, up to 576 microg/day, elicited increased feeding in TB rats prior to or subsequent to the development of anorexia. In hypothalamus, ghrelin-infused TB rats exhibited significantly increased concentration of neuropeptide Y (NPY) as compared to saline-infused TB rats. Hypothalamic expression of NPY and agouti-related protein (AgRP) messenger RNA were elevated in ghrelin-infused TB rats as compared to NTB rats, but saline-infused TB rats also exhibited increased expression of AgRP. Proopiomelanocortin message was reduced in ghrelin-infused and saline-infused TB rats as compared to noninfused TB control rats. Although ghrelin infusion did not preserve muscle protein, a significant saving in body fat was observed in TB rats. Thus, the adiposity effects of ghrelin did not require an orexigenic response to the peptide. These results suggest that continuous ghrelin infusion may not be an effective treatment for cancer anorexia.
Chance
William T
WT
Research Service, Veterans Affairs Medical Center, Cincinnati, OH, USA. william.chance@uc.edu
Dayal
Ramesh
R
Friend
Lou Ann
LA
Thomas
Ingrid
I
Sheriff
Sulaiman
S
D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D001483:Base Sequence; D002100:Cachexia / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects*; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D009374:Neoplasms, Experimental; D009478:Neuropeptide Y / Q000097:blood*; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054369:Agouti-Related Protein; D054439:Ghrelin; D009478:Neuropeptide Y