Abstract

Nesfatin-1 is an 82-amino acid protein encoded by the nucleobindin2 gene. When injected intracerebroventricularly, nesfatin-1, via a melanocortin 3/4 receptor-dependent mechanism, potently decreased both food and water intakes and elevated mean arterial pressure in a dose-related manner. Because nesfatin-1 colocalized with oxytocin in hypothalamus and because nesfatin-1 had direct depolarizing effects on oxytocin-producing neurons in hypothalamic slice preparations, we hypothesized that the actions of nesfatin-1 required the presence of functional oxytocin receptors. We, therefore, pretreated conscious, unrestrained male rats with the oxytocin receptor antagonist, ornithine vasotocin (OVT), before treatment with nesfatin-1. We found that pretreatment with OVT reversed the effects of nesfatin-1 on both food and water intake and on mean arterial pressure, indicating that the central oxytocin system is a downstream mediator of these actions of nesfatin-1. Additionally, we found that OVT reversed the anorexigenic effect of α-melanocyte-stimulating hormone (α-MSH), suggesting that the central oxytocin system is downstream of the central melanocortin system. Taken together, these data suggest that nesfatin-1 acts through a serial neuronal circuit, in which nesfatin-1 activates the central melanocortin system, which, in turn, acts through the central oxytocin system, leading to an inhibition of food and water intake and an increase in mean arterial pressure. Copyright © 2010 the American Physiological Society.

Department(s)

Biological Sciences

Publication Status

Open Access

Comments

National Heart, Lung, and Blood Institute, Grant R01HL066023

Keywords and Phrases

Blood pressure; Food intake

International Standard Serial Number (ISSN)

1522-1490; 0363-6119

Document Type

Article - Journal

Document Version

Final Version

File Type

text

Language(s)

English

Rights

© 2025 American Physiological Society, All rights reserved.

Creative Commons Licensing

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Publication Date

01 Jun 2010

PubMed ID

20335376

Included in

Biology Commons

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