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Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice

Decades of studies have revealed molecular and neural circuit bases for body weight homeostasis. Neural hormone oxytocin (Oxt) has received attention in this context because it is produced by neurons in the paraventricular hypothalamic nucleus (PVH), a known output center of hypothalamic regulation...

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Autores principales: Inada, Kengo, Tsujimoto, Kazoku, Yoshida, Masahide, Nishimori, Katsuhiko, Miyamichi, Kazunari
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9596155/
https://www.ncbi.nlm.nih.gov/pubmed/36281647
http://dx.doi.org/10.7554/eLife.75718
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author Inada, Kengo
Tsujimoto, Kazoku
Yoshida, Masahide
Nishimori, Katsuhiko
Miyamichi, Kazunari
author_facet Inada, Kengo
Tsujimoto, Kazoku
Yoshida, Masahide
Nishimori, Katsuhiko
Miyamichi, Kazunari
author_sort Inada, Kengo
collection PubMed
description Decades of studies have revealed molecular and neural circuit bases for body weight homeostasis. Neural hormone oxytocin (Oxt) has received attention in this context because it is produced by neurons in the paraventricular hypothalamic nucleus (PVH), a known output center of hypothalamic regulation of appetite. Oxt has an anorexigenic effect, as shown in human studies, and can mediate satiety signals in rodents. However, the function of Oxt signaling in the physiological regulation of appetite has remained in question, because whole-body knockout (KO) of Oxt or Oxt receptor (Oxtr) has little effect on food intake. We herein show that acute conditional KO (cKO) of Oxt selectively in the adult PVH, but not in the supraoptic nucleus, markedly increases body weight and food intake, with an elevated level of plasma triglyceride and leptin. Intraperitoneal administration of Oxt rescues the hyperphagic phenotype of the PVH Oxt cKO model. Furthermore, we show that cKO of Oxtr selectively in the posterior hypothalamic regions, especially the arcuate hypothalamic nucleus, a primary center for appetite regulations, phenocopies hyperphagic obesity. Collectively, these data reveal that Oxt signaling in the arcuate nucleus suppresses excessive food intake.
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spelling pubmed-95961552022-10-26 Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice Inada, Kengo Tsujimoto, Kazoku Yoshida, Masahide Nishimori, Katsuhiko Miyamichi, Kazunari eLife Genetics and Genomics Decades of studies have revealed molecular and neural circuit bases for body weight homeostasis. Neural hormone oxytocin (Oxt) has received attention in this context because it is produced by neurons in the paraventricular hypothalamic nucleus (PVH), a known output center of hypothalamic regulation of appetite. Oxt has an anorexigenic effect, as shown in human studies, and can mediate satiety signals in rodents. However, the function of Oxt signaling in the physiological regulation of appetite has remained in question, because whole-body knockout (KO) of Oxt or Oxt receptor (Oxtr) has little effect on food intake. We herein show that acute conditional KO (cKO) of Oxt selectively in the adult PVH, but not in the supraoptic nucleus, markedly increases body weight and food intake, with an elevated level of plasma triglyceride and leptin. Intraperitoneal administration of Oxt rescues the hyperphagic phenotype of the PVH Oxt cKO model. Furthermore, we show that cKO of Oxtr selectively in the posterior hypothalamic regions, especially the arcuate hypothalamic nucleus, a primary center for appetite regulations, phenocopies hyperphagic obesity. Collectively, these data reveal that Oxt signaling in the arcuate nucleus suppresses excessive food intake. eLife Sciences Publications, Ltd 2022-10-25 /pmc/articles/PMC9596155/ /pubmed/36281647 http://dx.doi.org/10.7554/eLife.75718 Text en © 2022, Inada et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Genetics and Genomics
Inada, Kengo
Tsujimoto, Kazoku
Yoshida, Masahide
Nishimori, Katsuhiko
Miyamichi, Kazunari
Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice
title Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice
title_full Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice
title_fullStr Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice
title_full_unstemmed Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice
title_short Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice
title_sort oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice
topic Genetics and Genomics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9596155/
https://www.ncbi.nlm.nih.gov/pubmed/36281647
http://dx.doi.org/10.7554/eLife.75718
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