Involvement of stomach ghrelin and hypothalamic neuropeptides in tumor necrosis factor-alpha-induced hypophagia in mice.
This study aimed to clarify the interaction of tumor necrosis factor-alpha (TNF-alpha), an anorexigenic cytokine, with ghrelin, an orexigenic peptide secreted by the stomach lining, and hypothalamic neuropeptides in the regulation of food intake in mice. The peripheral administration of TNF-alpha dose-dependently decreased the 24-h cumulative food intake compared with the administration of saline. Reduced food intake was observed at 6 h and 24 h. The same TNF-alpha treatment significantly decreased the plasma level of ghrelin at 6 h and 24 h after treatment compared with the control levels. These changes were accompanied by a significant reduction in the expression of ghrelin mRNA in the stomach at 24 h after treatment. TNF-alpha treatment also resulted in a significant increase in expression of pro-opiomelanocortin (POMC) mRNA and a significant decrease in expression of agouti-related protein (AGRP) mRNA in the hypothalamus at 6 h after treatment. Finally, the pre-administration of ghrelin, reversed the TNF-alpha-induced hypophagia in mice at 6 and 24 h. Taken together, these findings suggest that hypothalamic POMC and AGRP and stomach ghrelin may be involved in TNF-alpha-induced hypophagia in mice.
Endo
Mizuki
M
Department of Internal Medicine 1, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Yufu-Hasama, Oita, 879-5593 Japan.
Masaki
Takayuki
T
Seike
Masataka
M
Yoshimatsu
Hironobu
H
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005753:Gastric Mucosa / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D054439:Ghrelin; D006801:Humans; D006963:Hyperphagia / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000235:genetics*; D036361:Peptide Hormones / Q000097:blood / Q000235:genetics* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D054439:Ghrelin; D009479:Neuropeptides; D036361:Peptide Hormones; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha