Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: A route for ameliorating hyperphagia and obesity
Abstract
Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt suppresses feeding and, when infused subchronically, ameliorates hyperphagic obesity. However, the route through which peripheral Oxt informs the brain is obscure. This study aimed to explore whether vagal afferents mediate the sensing and anorexigenic effect of peripherally injected Oxt in mice. Intraperitoneal Oxt injection suppressed food intake and increased c-Fos expression in nucleus tractus solitarius to which vagal afferents project. The Oxt-induced feeding suppression and c-Fos expression in nucleus tractus solitarius were blunted in mice whose vagal afferent nerves were blocked by subdiaphragmatic vagotomy or capsaicin treatment. Oxt induced membrane depolarization and increases in cytosolic Ca(2+) concentration ([Ca(2+)]i) in single vagal afferent neurons. The Oxt-induced [Ca(2+)]i increases were markedly suppressed by Oxt receptor antagonist. These Oxt-responsive neurons also responded to cholecystokinin-8 and contained cocaine- and amphetamine-regulated transcript. In obese diabetic db/db mice, leptin failed to increase, but Oxt increased [Ca(2+)]i in vagal afferent neurons, and single or subchronic infusion of Oxt decreased food intake and body weight gain. These results demonstrate that peripheral Oxt injection suppresses food intake by activating vagal afferent neurons and thereby ameliorates obesity in leptin-resistant db/db mice. The peripheral Oxt-regulated vagal afferent neuron provides a novel target for treating hyperphagia and obesity.
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Oxytocin regulates feeding and metabolism at several sites, and its receptors are present throughout the gastrointestinal tract and on gastric vagal nerve endings.
“Oxytocin regulates feeding and metabolism at multiple sites (34,35).Its receptors are expressed throughout the gastrointestinal tract, and on gastric vagal nerve endings (36).”
From Intranasal Oxytocin: Myths and Delusions (2016) · cites this paper as [36]
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- Authors
- Iwasaki, Y., Maejima, Y., Suyama, S., Yoshida, M., Arai, T., Katsurada, K., Kumari, P., Nakabayashi, H., Kakei, M., & Yada, T.
- Affiliations
- Jichi Medical University (JP)
- Division of Integrative Physiology, Department of Physiology, Jichi Medical University School of Medicine, Tochigi, Japan;
- Kanazawa University (JP)
- Corresponding author
- Yada, Toshihiko
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2015-03-01
- Volume
- 308
- Issue
- 5
- Pages
- R360-R369
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2164232724
- Cited by
- 148
- References
- 56
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 5 · 2023: 8 · 2022: 12 · 2021: 28 · 2020: 11 · 2019: 14 · 2018: 17 · 2017: 13 · 2016: 12 · 2015: 9
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (22790218, 26670453)
- Japan Society for the Promotion of Science (JSPS) (24790221, 24591341, 23126523, 23390044)
- Jichi Medical University young investigator award
- The Naito Foundation
- Memorial Foundation for Female Natural Scientists
- Kowa Life Science Foundation
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT) (10036069)
- MEXT-Supported Programs for Strategic Research Foundation at Private Univesityies
- Japan Diabetes Foundation
- Salt Science Research Foundation (1434)
- KEIRIN RACE
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- oxytocin, vagal afferent neurons, feeding inhibition, hyperphagia, obesity, leptin resistance, nucleus tractus solitarius, vagotomy, capsaicin, intracellular calcium, c-fos, cholecystokinin-8, cocaine- and amphetamine-regulated transcript, db/db mice, food intake regulation
- MeSH terms
- Action Potentials, Animals, Appetite Depressants, Calcium, Disease Models, Animal, Dose-Response Relationship, Drug, Eating, Feeding Behavior, Hyperphagia, Injections, Intraperitoneal, Male, Mice, Inbred C57BL, Mice, Inbred ICR, Neurons, Afferent, Obesity, Oxytocin, Time Factors, Vagotomy, Vagus Nerve, Weight Gain, Down-Regulation, Proto-Oncogene Proteins c-fos, Solitary Nucleus, Sensory System Agents, Anti-Obesity Agents
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