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GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice
It is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated that optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake and/or energy expenditure (EE). However,...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468093/ https://www.ncbi.nlm.nih.gov/pubmed/37594983 http://dx.doi.org/10.1371/journal.pbio.3002252 |
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author | Oh, Youjin Yoo, Eun-Seon Ju, Sang Hyeon Kim, Eunha Lee, Seulgi Kim, Seyun Wickman, Kevin Sohn, Jong-Woo |
author_facet | Oh, Youjin Yoo, Eun-Seon Ju, Sang Hyeon Kim, Eunha Lee, Seulgi Kim, Seyun Wickman, Kevin Sohn, Jong-Woo |
author_sort | Oh, Youjin |
collection | PubMed |
description | It is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated that optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake and/or energy expenditure (EE). However, little is known about intrinsic molecules regulating NPY/AgRP neuronal excitability to affect long-term metabolic function. Here, we found that the G protein-gated inwardly rectifying K(+) (GIRK) channels are key to stabilize NPY/AgRP neurons and that NPY/AgRP neuron-selective deletion of the GIRK2 subunit results in a persistently increased excitability of the NPY/AgRP neurons. Interestingly, increased body weight and adiposity observed in the NPY/AgRP neuron-selective GIRK2 knockout mice were due to decreased sympathetic activity and EE, while food intake remained unchanged. The conditional knockout mice also showed compromised adaptation to coldness. In summary, our study identified GIRK2 as a key determinant of NPY/AgRP neuronal excitability and driver of EE in physiological and stress conditions. |
format | Online Article Text |
id | pubmed-10468093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-104680932023-08-31 GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice Oh, Youjin Yoo, Eun-Seon Ju, Sang Hyeon Kim, Eunha Lee, Seulgi Kim, Seyun Wickman, Kevin Sohn, Jong-Woo PLoS Biol Research Article It is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated that optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake and/or energy expenditure (EE). However, little is known about intrinsic molecules regulating NPY/AgRP neuronal excitability to affect long-term metabolic function. Here, we found that the G protein-gated inwardly rectifying K(+) (GIRK) channels are key to stabilize NPY/AgRP neurons and that NPY/AgRP neuron-selective deletion of the GIRK2 subunit results in a persistently increased excitability of the NPY/AgRP neurons. Interestingly, increased body weight and adiposity observed in the NPY/AgRP neuron-selective GIRK2 knockout mice were due to decreased sympathetic activity and EE, while food intake remained unchanged. The conditional knockout mice also showed compromised adaptation to coldness. In summary, our study identified GIRK2 as a key determinant of NPY/AgRP neuronal excitability and driver of EE in physiological and stress conditions. Public Library of Science 2023-08-18 /pmc/articles/PMC10468093/ /pubmed/37594983 http://dx.doi.org/10.1371/journal.pbio.3002252 Text en © 2023 Oh et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Oh, Youjin Yoo, Eun-Seon Ju, Sang Hyeon Kim, Eunha Lee, Seulgi Kim, Seyun Wickman, Kevin Sohn, Jong-Woo GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice |
title | GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice |
title_full | GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice |
title_fullStr | GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice |
title_full_unstemmed | GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice |
title_short | GIRK2 potassium channels expressed by the AgRP neurons decrease adiposity and body weight in mice |
title_sort | girk2 potassium channels expressed by the agrp neurons decrease adiposity and body weight in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10468093/ https://www.ncbi.nlm.nih.gov/pubmed/37594983 http://dx.doi.org/10.1371/journal.pbio.3002252 |
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