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Y1 and Y5 Receptors Are Both Required for the Regulation of Food Intake and Energy Homeostasis in Mice
Neuropeptide Y (NPY) acting in the hypothalamus is one of the most powerful orexigenic agents known. Of the five known Y receptors, hypothalamic Y1 and Y5 have been most strongly implicated in mediating hyperphagic effects. However, knockout of individual Y1 or Y5 receptors induces late-onset obesit...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387009/ https://www.ncbi.nlm.nih.gov/pubmed/22768253 http://dx.doi.org/10.1371/journal.pone.0040191 |
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author | Nguyen, Amy D. Mitchell, Natalie F. Lin, Shu Macia, Laurence Yulyaningsih, Ernie Baldock, Paul A. Enriquez, Ronaldo F. Zhang, Lei Shi, Yan-Chuan Zolotukhin, Serge Herzog, Herbert Sainsbury, Amanda |
author_facet | Nguyen, Amy D. Mitchell, Natalie F. Lin, Shu Macia, Laurence Yulyaningsih, Ernie Baldock, Paul A. Enriquez, Ronaldo F. Zhang, Lei Shi, Yan-Chuan Zolotukhin, Serge Herzog, Herbert Sainsbury, Amanda |
author_sort | Nguyen, Amy D. |
collection | PubMed |
description | Neuropeptide Y (NPY) acting in the hypothalamus is one of the most powerful orexigenic agents known. Of the five known Y receptors, hypothalamic Y1 and Y5 have been most strongly implicated in mediating hyperphagic effects. However, knockout of individual Y1 or Y5 receptors induces late-onset obesity – and Y5 receptor knockout also induces hyperphagia, possibly due to redundancy in functions of these genes. Here we show that food intake in mice requires the combined actions of both Y1 and Y5 receptors. Germline Y1Y5 ablation in Y1Y5(−/−) mice results in hypophagia, an effect that is at least partially mediated by the hypothalamus, since mice with adult-onset Y1Y5 receptor dual ablation targeted to the paraventricular nucleus (PVN) of the hypothalamus (Y1Y5(Hyp/Hyp)) also exhibit reduced spontaneous or fasting-induced food intake when fed a high fat diet. Interestingly, despite hypophagia, mice with germline or hypothalamus-specific Y1Y5 deficiency exhibited increased body weight and/or increased adiposity, possibly due to compensatory responses to gene deletion, such as the decreased energy expenditure observed in male Y1Y5(−/−) animals relative to wildtype values. While Y1 and Y5 receptors expressed in other hypothalamic areas besides the PVN – such as the dorsomedial nucleus and the ventromedial hypothalamus – cannot be excluded from having a role in the regulation of food intake, these studies demonstrate the pivotal, combined role of both Y1 and Y5 receptors in the mediation of food intake. |
format | Online Article Text |
id | pubmed-3387009 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33870092012-07-05 Y1 and Y5 Receptors Are Both Required for the Regulation of Food Intake and Energy Homeostasis in Mice Nguyen, Amy D. Mitchell, Natalie F. Lin, Shu Macia, Laurence Yulyaningsih, Ernie Baldock, Paul A. Enriquez, Ronaldo F. Zhang, Lei Shi, Yan-Chuan Zolotukhin, Serge Herzog, Herbert Sainsbury, Amanda PLoS One Research Article Neuropeptide Y (NPY) acting in the hypothalamus is one of the most powerful orexigenic agents known. Of the five known Y receptors, hypothalamic Y1 and Y5 have been most strongly implicated in mediating hyperphagic effects. However, knockout of individual Y1 or Y5 receptors induces late-onset obesity – and Y5 receptor knockout also induces hyperphagia, possibly due to redundancy in functions of these genes. Here we show that food intake in mice requires the combined actions of both Y1 and Y5 receptors. Germline Y1Y5 ablation in Y1Y5(−/−) mice results in hypophagia, an effect that is at least partially mediated by the hypothalamus, since mice with adult-onset Y1Y5 receptor dual ablation targeted to the paraventricular nucleus (PVN) of the hypothalamus (Y1Y5(Hyp/Hyp)) also exhibit reduced spontaneous or fasting-induced food intake when fed a high fat diet. Interestingly, despite hypophagia, mice with germline or hypothalamus-specific Y1Y5 deficiency exhibited increased body weight and/or increased adiposity, possibly due to compensatory responses to gene deletion, such as the decreased energy expenditure observed in male Y1Y5(−/−) animals relative to wildtype values. While Y1 and Y5 receptors expressed in other hypothalamic areas besides the PVN – such as the dorsomedial nucleus and the ventromedial hypothalamus – cannot be excluded from having a role in the regulation of food intake, these studies demonstrate the pivotal, combined role of both Y1 and Y5 receptors in the mediation of food intake. Public Library of Science 2012-06-29 /pmc/articles/PMC3387009/ /pubmed/22768253 http://dx.doi.org/10.1371/journal.pone.0040191 Text en Nguyen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Nguyen, Amy D. Mitchell, Natalie F. Lin, Shu Macia, Laurence Yulyaningsih, Ernie Baldock, Paul A. Enriquez, Ronaldo F. Zhang, Lei Shi, Yan-Chuan Zolotukhin, Serge Herzog, Herbert Sainsbury, Amanda Y1 and Y5 Receptors Are Both Required for the Regulation of Food Intake and Energy Homeostasis in Mice |
title | Y1 and Y5 Receptors Are Both Required for the Regulation of Food Intake and Energy Homeostasis in Mice |
title_full | Y1 and Y5 Receptors Are Both Required for the Regulation of Food Intake and Energy Homeostasis in Mice |
title_fullStr | Y1 and Y5 Receptors Are Both Required for the Regulation of Food Intake and Energy Homeostasis in Mice |
title_full_unstemmed | Y1 and Y5 Receptors Are Both Required for the Regulation of Food Intake and Energy Homeostasis in Mice |
title_short | Y1 and Y5 Receptors Are Both Required for the Regulation of Food Intake and Energy Homeostasis in Mice |
title_sort | y1 and y5 receptors are both required for the regulation of food intake and energy homeostasis in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387009/ https://www.ncbi.nlm.nih.gov/pubmed/22768253 http://dx.doi.org/10.1371/journal.pone.0040191 |
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