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Title: NEUROPEPTIDE Y RESTORES APPETITE, INCREASES CONCENTRATIONS OF GH AFTER CENTRAL INJECTION, BUT SUPPRESSES GH-RELEASING FACTOR-INDUCED RELEASE OF GHIN ENDOTOXIC SHEEP

Author
item MCMAHON, C. - AUBURN UNIV/AUBURN, AL
item BUXTON, D. - AUBURN UNIV/AUBURN, AL
item Elsasser, Theodore
item GUNTER, T. - AUBURN UNIV/AUBURN, AL
item SANDERS, L. - AUBURN UNIV/AUBURN, AL
item STEELE, B. - AUBURN UNVI/AUBURN, AL
item SARTIN, J. - AUBURN UNIV/AUBURN, AL

Submitted to: Journal of Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/19/1999
Publication Date: N/A
Citation: N/A

Interpretive Summary: One of the main problems of bacterial infection is the loss of appetite and associated weight loss. Because food intake is largely regulated at the level of the brain and is thought to involve a brain peptide called neuropeptide Y (NPY) we studies how the administration of NPY to sheep challenged with a bacterial toxin affected the recovery outcome. The administration of the toxin resulted in a significant decrease in food intake, altered patterns of growth hormone secretion and an overall decrease in another hormone called IGF-I. The administration of NPY reversed several of the negative effects of the bacterial toxin and improved the outcome of the simulated disease state. These results suggest that some pharmacological drugs that alter NPY in the brain might be beneficial to increase appetite during illness.

Technical Abstract: The objective of this study was to determine whether neuropeptide Y (NPY) and recombinant human interleukin-1 receptor antagonist (ILRA) would restore appetite and block changes in concentrations of GH, NEFA, and IGF-I during experimental endotoxemia in sheep. Six treatments were given to castrate male sheep in a 6 X 6 Latin-square design. Each sheep was infused for 3 days with either vehicle (0.9% saline) or endotoxin (20 micrograms/kg/d) via implanted osmotic minipumps. Twenty-four hours later, one of 3 treatments were further administered: artificial cerebrospinal fluid, NPY, or ILRA). GHRH was injected at the 6 hr point and repeated blood samples obtained. On day 1 NPY restored feed intake in LPS-sheep and induced hyperphagia in nonLPS-sheep. In contrast, ILRA did not affect appetite. NPY suppressed GHRH-induced GH release. Concentrations of IGF-I were 20% higher in LPS-NPY sheep than sheep given LPS alone. We conclude that inappetance during endotoxemia or some forms of disease stress is due to down-regulation of an NPY mechanism. Furthermore, NPY may play a role in regulating GH secretion during illness and healthy states.