Decreased plasma ghrelin contributes to anorexia following novelty stress

作者:Saegusa Yayoi; Takeda Hiroshi*; Muto Shuichi; Nakagawa Koji; Ohnishi Shunsuke; Sadakane Chiharu; Nahata Miwa; Hattori Tomohisa; Asaka Masahiro
来源:American Journal of Physiology - Endocrinology And Metabolism, 2011, 301(4): E685-E696.
DOI:10.1152/ajpendo.00121.2011

摘要

Saegusa Y, Takeda H, Muto S, Nakagawa K, Ohnishi S, Sadakane C, Nahata M, Hattori T, Asaka M. Decreased plasma ghrelin contributes to anorexia following novelty stress. Am J Physiol Endocrinol Metab 301: E685-E696, 2011. First published June 28, 2011; doi:10.1152/ajpendo.00121.2011.-We hypothesized that anorexia induced by novelty stress caused by exposure to a novel environment may be due to activation of corticotropin-releasing factor (CRF) and subsequently mediated by decreasing peripheral ghrelin concentration via serotonin (5-HT) and melanocortin-4 receptors (MC4R). Each mouse was transferred from group-housed cages to individual cages to establish the novelty stress. We observed the effect of changes in feeding behavior in a novel environment using the method of transferring group-housed mice to individual cages. We investigated the effect of an intracerebroventricular injection of antagonists/agonists of CRF1/2 receptors (CRF1/2Rs), 5-HT(1B/2C) receptors (5-HT(1B/2C)R), and MC4R to clarify the role of each receptor on the decrease in food intake. Plasma ghrelin levels were also measured. The novelty stress caused a reduction in food intake that was abolished by administering a CRF1R antagonist. Three hours after the novelty stress, appetite reduction was associated with reduced levels of neuropeptide Y/agouti-related peptide mRNA, increased levels of proopiomelanocortin mRNA in the hypothalamus, and a decrease in plasma ghrelin level. Administering a CRF1R antagonist, a 5-HT(1B/2C)R antagonist, an MC4R antagonist, exogenous ghrelin, and an enhancer of ghrelin secretion, rikkunshito, resolved the reduction in food intake 3 h after the novelty stress by enhancing circulating ghrelin concentrations. We showed that anorexia during a novelty stress is a process in which CRF1R is activated at the early stage of appetite loss and is subsequently activated by a 5-HT(1B/2C)R and MC4R stimulus, leading to decreased peripheral ghrelin concentrations.

  • 出版日期2011-10