Decreased plasma ghrelin contributes to anorexia following novelty stress

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.

Pathophysiologic Basis of Anorexia: Focus on the Interaction between Ghrelin Dynamics and the Serotonergic System

“…53) We have recently determined that CRFR1 is also involved in the regulation of ghrelin secretion. Using a novelty stress model, 54) we found that 3 h after the novelty stress, appetite reduction was associated with a decrease in the plasma ghrelin level. 55) Administering a CRF1R selective antagonist, but not a CRF2R antagonist, resolved the reduction in food intake 3 h after the novelty stress by enhancing circulating ghrelin concentrations.…”

“…Interestingly, 5-HT 1B and 5-HT 2C receptor antagonists and melanocortin-4 (MC4) receptor antagonist alleviated the novelty stress-induced hypophagia and the reduction in circulating ghrelin levels. 55) Moreover, intracerebroventricular administration of the 5-HT 1B/2CR agonist mCPP suppressed the plasma acylated ghrelin level and food intake. 55) From these results, we hypothesize that acute appetite suppression due to CRF1R activation after a novelty stress is caused by a chain reaction of appetite control mechanisms mediated by 5-HT 1B/2C receptors in the arcuate nucleus to MC4 receptor system in the paraventricular nucleus, causing lowered peripheral ghrelin secretion.…”

Effects of Isolation and Social Subchronic Stresses on Food Intake and Levels of Leptin, Ghrelin, and Glucose in Male Rats

“…reported that the serum ghrelin level decreased after 7 days of novelty stress. [43] They suggested the increases in CRH resulted in a declined ghrelin level, leading to the sustained food intake reduction. [43] However, other researches indicated an opposite finding between the ghrelin level and food intake.…”

“…[43] They suggested the increases in CRH resulted in a declined ghrelin level, leading to the sustained food intake reduction. [43] However, other researches indicated an opposite finding between the ghrelin level and food intake. [444546] Some previous studies demonstrated that the elevated serum ghrelin level helps to an individual for adaptation to chronic stress but at the expense of increased eating food.…”

Gut-Brain Neuroendocrine Signaling Under Conditions of Stress—Focus on Food Intake-Regulatory Mediators

“…Chronic inflammatory stress elicited by adjuvant-induced arthritis in rats or rheumatoid arthritis in humans reduces circulating ghrelin levels (59). There are also reports that a psychological stressor such as novelty stress in mice decreases plasma levels of ghrelin and food intake, alterations prevented by rikkunshito (60, 61). Chronic restraint stress or exposure to foot-shock downregulates ghrelin mRNA expression in the mouse hypothalamus (62) and reduces plasma levels of ghrelin in rats (63).…”