Acute and repeated restraint differentially activate orexigenic pathways in the rat hypothalamus
Open accessAbstract
Stress and obesity are highly prevalent conditions, and the mechanisms through which stress affects food intake are complex. In the present study, stress-induced activation in neuropeptide systems controlling ingestive behavior was determined. Adult male rats were exposed to acute (30 min/d × 1 d) or repeated (30 min/d × 14 d) restraint stress, followed by transcardial perfusion 2 h after the termination of the stress exposure. Brain tissues were harvested, and 30 μm sections through the hypothalamus were immunohistochemically stained for Fos protein, which was then co-localized within neurons staining positively for the type 4 melanocortin receptor (MC4R), the glucagon-like peptide-1 receptor (GLP1R), or agouti-related peptide (AgRP). Cell counts were performed in the paraventricular (PVH), arcuate (ARC) and ventromedial (VMH) hypothalamic nuclei and in the lateral hypothalamic area (LHA). Fos was significantly increased in all regions except the VMH in acutely stressed rats, and habituated with repeated stress exposure, consistent with previous studies. In the ARC, repeated stress reduced MC4R cell activation while acute restraint decreased activation in GLP1R neurons. Both patterns of stress exposure reduced the number of AgRP-expressing cells that also expressed Fos in the ARC. Acute stress decreased Fos-GLP1R expression in the LHA, while repeated restraint increased the number of Fos-AgRP neurons in this region. The overall profile of orexigenic signaling in the brain is thus enhanced by acute and repeated restraint stress, with repeated stress leading to further increases in signaling, in a region-specific manner. Stress-induced modifications to feeding behavior appear to depend on both the duration of stress exposure and regional activation in the brain. These results suggest that food intake may be increased as a consequence of stress, and may play a role in obesity and other stress-associated metabolic disorders.
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Neurons in the arcuate nucleus of the hypothalamus are activated by emotional stimuli.
“We and others have previously shown that neurons in the arcuate nucleus (ARC) of the hypothalamus are activated by emotional stimuli [16, 17].”
From Chronic unpredictable stress induces depression-related behaviors by suppressing AgRP neuron activity (2021) · cites this paper as [17]
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- Authors
- Chagra, S. L., Zavala, J. K., Hall, M. V., & Gosselink, K. L.
- Affiliations
- The University of Texas at El Paso (US)
- Corresponding author
- Gosselink, Kristin L.
- Venue
- Regulatory Peptides
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 167
- Issue
- 1
- Pages
- 70-78
- ISSN
- 0167-0115 (ISSN-L)
- PMC
- PMC3042535
- OpenAlex
- W2039880126
- Cited by
- 35
- References
- 41
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 5 · 2016: 1 · 2015: 2 · 2014: 2 · 2013: 6 · 2012: 1
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Regulatory Peptides (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH
- NSF (0245071)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- restraint stress, acute stress, repeated stress, hypothalamus, orexigenic neurons, Fos expression, melanocortin-4 receptor, GLP-1 receptor, agouti-related protein, paraventricular nucleus, arcuate nucleus, ventromedial hypothalamus, lateral hypothalamus, obesity
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Animals, Appetite, Cell Count, Feeding Behavior, Habituation, Psychophysiologic, Heart, Hypothalamus, Immunohistochemistry, Male, Microtomy, Neurons, Obesity, Perfusion, Restraint, Physical, Stress, Physiological, Signal Transduction, Gene Expression, Proto-Oncogene Proteins c-fos, Receptors, Glucagon, Receptor, Melanocortin, Type 4, Rats, Agouti-Related Protein
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