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SUN-269 Activation of GFRAL Neurons Decreases Food Intake via Aversive Pathways
Growth and differentiation factor 15 (GDF15), an anorexigenic peptide that represents a promising candidate for anti-obesity treatment, acts via GDNF Family Receptor Alpha Like (GFRAL), which is expressed almost exclusively on a subset of neurons in the area postrema (AP). To determine the function...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207650/ http://dx.doi.org/10.1210/jendso/bvaa046.1272 |
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author | Sabatini, Paul Frikke-Schmidt, Henriette Rupp, Alan Gordian, Desiree Myers Jr, Martin Seeley, Randy John |
author_facet | Sabatini, Paul Frikke-Schmidt, Henriette Rupp, Alan Gordian, Desiree Myers Jr, Martin Seeley, Randy John |
author_sort | Sabatini, Paul |
collection | PubMed |
description | Growth and differentiation factor 15 (GDF15), an anorexigenic peptide that represents a promising candidate for anti-obesity treatment, acts via GDNF Family Receptor Alpha Like (GFRAL), which is expressed almost exclusively on a subset of neurons in the area postrema (AP). To determine the function and mechanisms of action for GFRAL neurons, we generated Gfral(cre) and conditional Gfral(CreERT) mice. Although their chemogenetic (DREADD-mediated) activation promoted FOS in a variety of brainstem, hypothalamic, and limbic nuclei, GFRAL neurons projected only to the nucleus of the solitary tract (NTS) and the parabrachial nucleus (PBN), where they innervated and activated aversive/anorexigenic GCRP-expressing cells. Tetanus-toxin-mediated silencing of PBN CGRP neurons abrogated the aversive and anorexic effects of GDF15. Furthermore, while non-gastrointestinal (GI) stimuli (e.g., GDF15 and LPS, but not feeding or gut peptide mimetics) activated GFRAL neurons, chemogenetically activating these cells decreased gastric emptying, suppressed feeding, and promoted a conditioned taste aversion. These findings suggest that GFRAL neurons link non-GI anorexigenic signals to the control of gut physiology and to the aversive suppression of food intake. Additionally, because the chemogenetic activation of GFRAL neurons suppressed food intake more strongly than GDF15 in lean mice, additional modes of activating GFRAL neurons may augment the anorectic potential of GDF15. |
format | Online Article Text |
id | pubmed-7207650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-72076502020-05-13 SUN-269 Activation of GFRAL Neurons Decreases Food Intake via Aversive Pathways Sabatini, Paul Frikke-Schmidt, Henriette Rupp, Alan Gordian, Desiree Myers Jr, Martin Seeley, Randy John J Endocr Soc Neuroendocrinology and Pituitary Growth and differentiation factor 15 (GDF15), an anorexigenic peptide that represents a promising candidate for anti-obesity treatment, acts via GDNF Family Receptor Alpha Like (GFRAL), which is expressed almost exclusively on a subset of neurons in the area postrema (AP). To determine the function and mechanisms of action for GFRAL neurons, we generated Gfral(cre) and conditional Gfral(CreERT) mice. Although their chemogenetic (DREADD-mediated) activation promoted FOS in a variety of brainstem, hypothalamic, and limbic nuclei, GFRAL neurons projected only to the nucleus of the solitary tract (NTS) and the parabrachial nucleus (PBN), where they innervated and activated aversive/anorexigenic GCRP-expressing cells. Tetanus-toxin-mediated silencing of PBN CGRP neurons abrogated the aversive and anorexic effects of GDF15. Furthermore, while non-gastrointestinal (GI) stimuli (e.g., GDF15 and LPS, but not feeding or gut peptide mimetics) activated GFRAL neurons, chemogenetically activating these cells decreased gastric emptying, suppressed feeding, and promoted a conditioned taste aversion. These findings suggest that GFRAL neurons link non-GI anorexigenic signals to the control of gut physiology and to the aversive suppression of food intake. Additionally, because the chemogenetic activation of GFRAL neurons suppressed food intake more strongly than GDF15 in lean mice, additional modes of activating GFRAL neurons may augment the anorectic potential of GDF15. Oxford University Press 2020-05-08 /pmc/articles/PMC7207650/ http://dx.doi.org/10.1210/jendso/bvaa046.1272 Text en © Endocrine Society 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Neuroendocrinology and Pituitary Sabatini, Paul Frikke-Schmidt, Henriette Rupp, Alan Gordian, Desiree Myers Jr, Martin Seeley, Randy John SUN-269 Activation of GFRAL Neurons Decreases Food Intake via Aversive Pathways |
title | SUN-269 Activation of GFRAL Neurons Decreases Food Intake via Aversive Pathways |
title_full | SUN-269 Activation of GFRAL Neurons Decreases Food Intake via Aversive Pathways |
title_fullStr | SUN-269 Activation of GFRAL Neurons Decreases Food Intake via Aversive Pathways |
title_full_unstemmed | SUN-269 Activation of GFRAL Neurons Decreases Food Intake via Aversive Pathways |
title_short | SUN-269 Activation of GFRAL Neurons Decreases Food Intake via Aversive Pathways |
title_sort | sun-269 activation of gfral neurons decreases food intake via aversive pathways |
topic | Neuroendocrinology and Pituitary |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207650/ http://dx.doi.org/10.1210/jendso/bvaa046.1272 |
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