Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 308, Issue 5, Pages R360-R369Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00344.2014
Keywords
nodose ganglion; oxytocin; food intake; obesity; leptin
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [22790218, 24790221]
- Jichi Medical University Young Investigator Award
- The Naito Foundation
- JSPS [24591341, 23126523, 23390044, 26670453]
- Memorial Foundation for Female Natural Scientists
- Kowa Life Science Foundation
- Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) [10036069]
- MEXT-Supported Programs for Strategic Research Foundation at Private Universities (Cooperative Basic and Clinical Research on Circadian Medicine) [20132017]
- Health Labor Sciences Research Grants from the Ministry of Health, Labor, and Welfare, Japan
- Japan Diabetes Foundation
- Salt Science Research Foundation [1434]
- Grants-in-Aid for Scientific Research [23126523, 24790221, 22790218, 24591341] Funding Source: KAKEN
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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 Ca2+ concentration ([Ca2+] (i)) in single vagal afferent neurons. The Oxt-induced [Ca2+] i increases were markedly suppressed by Oxt receptor antagonist. These Oxt-responsive neurons also responded to chole-cystokinin-8 and contained cocaine- and amphetamine-regulated transcript. In obese diabetic db/db mice, leptin failed to increase, but Oxt increased [Ca2+] 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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