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Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus–brainstem pathway

Early-life trauma (ELT) is a risk factor for binge eating and obesity later in life, yet the neural circuits that underlie this association have not been addressed. Here, we show in mice that downregulation of the leptin receptor (Lepr) in the lateral hypothalamus (LH) and its effect on neural activ...

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Autores principales: Shin, Sora, You, In-Jee, Jeong, Minju, Bae, Yeeun, Wang, Xiao-Yun, Cawley, Mikel Leann, Han, Abraham, Lim, Byung Kook
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9829538/
https://www.ncbi.nlm.nih.gov/pubmed/36510113
http://dx.doi.org/10.1038/s41593-022-01208-0
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author Shin, Sora
You, In-Jee
Jeong, Minju
Bae, Yeeun
Wang, Xiao-Yun
Cawley, Mikel Leann
Han, Abraham
Lim, Byung Kook
author_facet Shin, Sora
You, In-Jee
Jeong, Minju
Bae, Yeeun
Wang, Xiao-Yun
Cawley, Mikel Leann
Han, Abraham
Lim, Byung Kook
author_sort Shin, Sora
collection PubMed
description Early-life trauma (ELT) is a risk factor for binge eating and obesity later in life, yet the neural circuits that underlie this association have not been addressed. Here, we show in mice that downregulation of the leptin receptor (Lepr) in the lateral hypothalamus (LH) and its effect on neural activity is crucial in causing ELT-induced binge-like eating and obesity upon high-fat diet exposure. We also found that the increased activity of Lepr-expressing LH (LH(Lepr)) neurons encodes sustained binge-like eating in ELT mice. Inhibition of LH(Lepr) neurons projecting to the ventrolateral periaqueductal gray normalizes these behavioral features of ELT mice. Furthermore, activation of proenkephalin-expressing ventrolateral periaqueductal gray neurons, which receive inhibitory inputs from LH(Lepr) neurons, rescues ELT-induced maladaptive eating habits. Our results identify a circuit pathway that mediates ELT-induced maladaptive eating and may lead to the identification of novel therapeutic targets for binge eating and obesity.
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spelling pubmed-98295382023-01-11 Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus–brainstem pathway Shin, Sora You, In-Jee Jeong, Minju Bae, Yeeun Wang, Xiao-Yun Cawley, Mikel Leann Han, Abraham Lim, Byung Kook Nat Neurosci Article Early-life trauma (ELT) is a risk factor for binge eating and obesity later in life, yet the neural circuits that underlie this association have not been addressed. Here, we show in mice that downregulation of the leptin receptor (Lepr) in the lateral hypothalamus (LH) and its effect on neural activity is crucial in causing ELT-induced binge-like eating and obesity upon high-fat diet exposure. We also found that the increased activity of Lepr-expressing LH (LH(Lepr)) neurons encodes sustained binge-like eating in ELT mice. Inhibition of LH(Lepr) neurons projecting to the ventrolateral periaqueductal gray normalizes these behavioral features of ELT mice. Furthermore, activation of proenkephalin-expressing ventrolateral periaqueductal gray neurons, which receive inhibitory inputs from LH(Lepr) neurons, rescues ELT-induced maladaptive eating habits. Our results identify a circuit pathway that mediates ELT-induced maladaptive eating and may lead to the identification of novel therapeutic targets for binge eating and obesity. Nature Publishing Group US 2022-12-12 2023 /pmc/articles/PMC9829538/ /pubmed/36510113 http://dx.doi.org/10.1038/s41593-022-01208-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Shin, Sora
You, In-Jee
Jeong, Minju
Bae, Yeeun
Wang, Xiao-Yun
Cawley, Mikel Leann
Han, Abraham
Lim, Byung Kook
Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus–brainstem pathway
title Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus–brainstem pathway
title_full Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus–brainstem pathway
title_fullStr Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus–brainstem pathway
title_full_unstemmed Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus–brainstem pathway
title_short Early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus–brainstem pathway
title_sort early adversity promotes binge-like eating habits by remodeling a leptin-responsive lateral hypothalamus–brainstem pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9829538/
https://www.ncbi.nlm.nih.gov/pubmed/36510113
http://dx.doi.org/10.1038/s41593-022-01208-0
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