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Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity

Obesity is the result of a long-term positive energy balance in which caloric intake overrides energy expenditure. This anabolic state results from the defective activity of hypothalamic neurons involved in the sensing and response to adiposity. However, it is currently unknown what the earliest obe...

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Autores principales: Souza, Gabriela F. P., Solon, Carina, Nascimento, Lucas F., De-Lima-Junior, Jose C., Nogueira, Guilherme, Moura, Rodrigo, Rocha, Guilherme Z., Fioravante, Milena, Bobbo, Vanessa, Morari, Joseane, Razolli, Daniela, Araujo, Eliana P., Velloso, Licio A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931679/
https://www.ncbi.nlm.nih.gov/pubmed/27373214
http://dx.doi.org/10.1038/srep29290
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author Souza, Gabriela F. P.
Solon, Carina
Nascimento, Lucas F.
De-Lima-Junior, Jose C.
Nogueira, Guilherme
Moura, Rodrigo
Rocha, Guilherme Z.
Fioravante, Milena
Bobbo, Vanessa
Morari, Joseane
Razolli, Daniela
Araujo, Eliana P.
Velloso, Licio A.
author_facet Souza, Gabriela F. P.
Solon, Carina
Nascimento, Lucas F.
De-Lima-Junior, Jose C.
Nogueira, Guilherme
Moura, Rodrigo
Rocha, Guilherme Z.
Fioravante, Milena
Bobbo, Vanessa
Morari, Joseane
Razolli, Daniela
Araujo, Eliana P.
Velloso, Licio A.
author_sort Souza, Gabriela F. P.
collection PubMed
description Obesity is the result of a long-term positive energy balance in which caloric intake overrides energy expenditure. This anabolic state results from the defective activity of hypothalamic neurons involved in the sensing and response to adiposity. However, it is currently unknown what the earliest obesity-linked hypothalamic defect is and how it orchestrates the energy imbalance present in obesity. Using an outbred model of diet-induced obesity we show that defective regulation of hypothalamic POMC is the earliest marker distinguishing obesity-prone from obesity-resistant mice. The early inhibition of hypothalamic POMC was sufficient to transform obesity-resistant in obesity-prone mice. In addition, the post-prandial change in the blood level of β-endorphin, a POMC-derived peptide, correlates with body mass gain in rodents and humans. Taken together, these results suggest that defective regulation of POMC expression, which leads to a change of β-endorphin levels, is the earliest hypothalamic defect leading to obesity.
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spelling pubmed-49316792016-07-06 Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity Souza, Gabriela F. P. Solon, Carina Nascimento, Lucas F. De-Lima-Junior, Jose C. Nogueira, Guilherme Moura, Rodrigo Rocha, Guilherme Z. Fioravante, Milena Bobbo, Vanessa Morari, Joseane Razolli, Daniela Araujo, Eliana P. Velloso, Licio A. Sci Rep Article Obesity is the result of a long-term positive energy balance in which caloric intake overrides energy expenditure. This anabolic state results from the defective activity of hypothalamic neurons involved in the sensing and response to adiposity. However, it is currently unknown what the earliest obesity-linked hypothalamic defect is and how it orchestrates the energy imbalance present in obesity. Using an outbred model of diet-induced obesity we show that defective regulation of hypothalamic POMC is the earliest marker distinguishing obesity-prone from obesity-resistant mice. The early inhibition of hypothalamic POMC was sufficient to transform obesity-resistant in obesity-prone mice. In addition, the post-prandial change in the blood level of β-endorphin, a POMC-derived peptide, correlates with body mass gain in rodents and humans. Taken together, these results suggest that defective regulation of POMC expression, which leads to a change of β-endorphin levels, is the earliest hypothalamic defect leading to obesity. Nature Publishing Group 2016-07-04 /pmc/articles/PMC4931679/ /pubmed/27373214 http://dx.doi.org/10.1038/srep29290 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Souza, Gabriela F. P.
Solon, Carina
Nascimento, Lucas F.
De-Lima-Junior, Jose C.
Nogueira, Guilherme
Moura, Rodrigo
Rocha, Guilherme Z.
Fioravante, Milena
Bobbo, Vanessa
Morari, Joseane
Razolli, Daniela
Araujo, Eliana P.
Velloso, Licio A.
Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity
title Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity
title_full Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity
title_fullStr Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity
title_full_unstemmed Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity
title_short Defective regulation of POMC precedes hypothalamic inflammation in diet-induced obesity
title_sort defective regulation of pomc precedes hypothalamic inflammation in diet-induced obesity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931679/
https://www.ncbi.nlm.nih.gov/pubmed/27373214
http://dx.doi.org/10.1038/srep29290
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