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Neuropeptide W-Induced Hypophagia is Mediated Through Corticotropin-Releasing Hormone-Containing Neurons

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Abstract

Neuropeptide W (NPW), which was originally isolated from the porcine hypothalamus, has been identified as the endogenous ligand for both the NPBWR1 (GPR7) and NPBWR2 (GPR8) receptors. These receptors, which belong to the orphan G protein-coupled receptor (GPCR) family, share a high sequence homology with the opioid and somatostatin receptor families. NPW and NPBWR1 are widely distributed in the rat central nervous system (CNS). While the intracerebroventricular (i.c.v.) injection of NPW elevates plasma corticosterone levels, the intravenous administration of NPW in conjunction with a corticotropin-releasing hormone (CRH) antagonist blocks NPW-induced corticosterone secretion. It has been reported that NPW is involved in regulating the hypothalamus-pituitary-adrenal cortex (HPA) axis and that i.c.v. administration of NPW decreases feeding behavior. The aim of the present study was to ascertain if NPW’s role in feeding regulation is mediated (or not) through corticotropin-releasing hormone (CRH)-containing neurons. We found that NPW-containing axon terminals make synapses with CRH-immunoreactive cell bodies and dendritic processes in the hypothalamic paraventricular nucleus (PVN). The central infusion of NPW significantly induced c-Fos expression in CRH-immunoreactive neurons in the mouse PVN, but not in vasopressin- or oxytocin-immunoreactive neurons. To determine if NPW regulates feeding behavior through CRH neurons, the feeding behavior of mice was studied following the i.c.v. administration NPW in the presence or absence of pretreatment with a CRH antagonist. While NPW administration decreased feeding activity, the CRH antagonist inhibited this effect. These results strongly suggest that NPW regulates feeding behavior through CRH neurons in the mouse brain.

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Acknowledgments

This study was supported in part by grants for the Grant-in-Aid for Scientific Research (C) and Grant-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to FT 26350912, HK 24590241, and SH 90644261). This study was supported in part by Grant-in-Aid for challenging Exploratory Research for the Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to SS 22126004). The study was also supported in part by Grant-in-Aid for Challenging Exploratory Research of Japan (to SS 25670767).

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Authors and Affiliations

  1. Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan

    Fumiko Takenoya, Lihua Wang, Haruaki Kageyama, Satoshi Hirako, Nobuhiro Wada, Junichi Sakagami, Naoko Nonaka & Seiji Shioda

  2. Department of Exercise and Sports Physiology, Hoshi University School of Pharmacy and Pharmaceutical Science, Shinagawa-ku, Tokyo, 142-8555, Japan

    Fumiko Takenoya

  3. Department of Nutrition, Faculty of Health Care, Kiryu University, Gunma, Japan

    Haruaki Kageyama

  4. Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

    Hirofumi Hashimoto & Yoichi Ueta

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  1. Fumiko Takenoya
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  2. Lihua Wang
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  9. Naoko Nonaka
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  10. Seiji Shioda
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Correspondence to Seiji Shioda.

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Takenoya, F., Wang, L., Kageyama, H. et al. Neuropeptide W-Induced Hypophagia is Mediated Through Corticotropin-Releasing Hormone-Containing Neurons. J Mol Neurosci 56, 789–798 (2015). https://doi.org/10.1007/s12031-015-0501-1

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  • DOI: https://doi.org/10.1007/s12031-015-0501-1

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