Decreased plasma ghrelin contributes to anorexia following novelty stress

Am J Physiol Endocrinol Metab. 2011 Oct;301(4):E685-96. doi: 10.1152/ajpendo.00121.2011. Epub 2011 Jun 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anorexia / blood*
  • Anorexia / etiology
  • Appetite / physiology
  • Corticotropin-Releasing Hormone / metabolism
  • Eating / physiology*
  • Feeding Behavior / physiology
  • Ghrelin / blood*
  • Hypothalamus / metabolism*
  • Mice
  • Pro-Opiomelanocortin / metabolism
  • Receptor, Melanocortin, Type 4 / metabolism
  • Receptor, Serotonin, 5-HT1B / metabolism
  • Receptor, Serotonin, 5-HT2C / metabolism
  • Receptors, Corticotropin-Releasing Hormone / metabolism
  • Stress, Psychological / blood*
  • Stress, Psychological / complications

Substances

  • Ghrelin
  • Receptor, Melanocortin, Type 4
  • Receptor, Serotonin, 5-HT1B
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Corticotropin-Releasing Hormone
  • Pro-Opiomelanocortin
  • Corticotropin-Releasing Hormone