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Ghrelin mediates stress-induced food-reward behavior in mice
Jen-Chieh Chuang, … , Michael Lutter, Jeffrey M. Zigman
Jen-Chieh Chuang, … , Michael Lutter, Jeffrey M. Zigman
Published June 23, 2011
Citation Information: J Clin Invest. 2011;121(7):2684-2692. https://doi.org/10.1172/JCI57660.
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Research Article Article has an altmetric score of 22

Ghrelin mediates stress-induced food-reward behavior in mice

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Abstract

The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense “comfort foods.” Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrating this response. Here, we describe a system in which food-reward behavior, assessed using a conditioned place preference (CPP) task, is monitored in mice after exposure to chronic social defeat stress (CSDS), a model of prolonged psychosocial stress, featuring aspects of major depression and posttraumatic stress disorder. Under this regime, CSDS increased both CPP for and intake of high-fat diet, and stress-induced food-reward behavior was dependent on signaling by the peptide hormone ghrelin. Also, signaling specifically in catecholaminergic neurons mediated not only ghrelin’s orexigenic, antidepressant-like, and food-reward behavioral effects, but also was sufficient to mediate stress-induced food-reward behavior. Thus, this mouse model has allowed us to ascribe a role for ghrelin-engaged catecholaminergic neurons in stress-induced eating.

Authors

Jen-Chieh Chuang, Mario Perello, Ichiro Sakata, Sherri Osborne-Lawrence, Joseph M. Savitt, Michael Lutter, Jeffrey M. Zigman

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Figure 3

Selective GHSR expression in catecholaminergic neurons is sufficient for several ghrelin-mediated actions.

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Selective GHSR expression in catecholaminergic neurons is sufficient for...
(A) Cre-mediated restoration of Ghsr mRNA expression is observed in brain regions of GHSR-null/TH mice containing catecholaminergic neurons programmed to express GHSRs, including the ARC and VTA, as determined using qRT-PCR (n = 6 per group). Mean ± SEM threshold cycle values for Ghsr mRNA in each brain site are denoted above the bars. (B) Ghrelin-induced acute food intake is partially restored in GHSR-null/TH mice. (*P < 0.05, ***P < 0.0001) (C) Fasting blood glucose levels are not restored to wild-type levels in GHSR-null/TH mice (*P < 0.05). (D) Administered ghrelin-induced CPP for HFD (**P < 0.005, ***P < 0.0001), (E) social interaction phenotype after CSDS (*P < 0.05), and (F) CSDS-induced CPP for HFD (*P = 0.042, **P = 0.020) are all restored to wild-type levels in GHSR-null/TH mice. For B–F, n = 19–30 wild-type mice (including 12–22 mice without and 5–14 mice with TH-cre), n = 14–34 GHSR-null mice, and n = 14–23 GHSR-null/TH mice. Significant effects of treatment (ghrelin vs. saline or ad libitum–fed versus 24-hour fast) and significant genotype X treatment interactions are indicated.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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