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Controlling hypothalamic DNA methylation at the Pomc promoter does not regulate weight gain during the development of obesity
Obesity is a complex medical condition that is linked to various health complications such as infertility, stroke, and osteoarthritis. Understanding the neurobiology of obesity is crucial for responding to the etiology of this disease. The hypothalamus coordinates many integral activities such as ho...
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/PMC10085038/ https://www.ncbi.nlm.nih.gov/pubmed/37036864 http://dx.doi.org/10.1371/journal.pone.0284286 |
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author | McFadden, Taylor Gaito, Natasha Carucci, Isabella Fletchall, Everett Farrell, Kayla Jarome, Timothy J. |
author_facet | McFadden, Taylor Gaito, Natasha Carucci, Isabella Fletchall, Everett Farrell, Kayla Jarome, Timothy J. |
author_sort | McFadden, Taylor |
collection | PubMed |
description | Obesity is a complex medical condition that is linked to various health complications such as infertility, stroke, and osteoarthritis. Understanding the neurobiology of obesity is crucial for responding to the etiology of this disease. The hypothalamus coordinates many integral activities such as hormone regulation and feed intake and numerous studies have observed altered hypothalamic gene regulation in obesity models. Previously, it was reported that the promoter region of the satiety gene, Pomc, has increased DNA methylation in the hypothalamus following short-term exposure to a high fat diet, suggesting that epigenetic-mediated repression of hypothalamic Pomc might contribute to the development of obesity. However, due to technical limitations, this has never been directly tested. Here, we used the CRISPR-dCas9-TET1 and dCas9-DNMT3a systems to test the role of Pomc DNA methylation in the hypothalamus in abnormal weight gain following acute exposure to a high fat diet in male rats. We found that exposure to a high fat diet increases Pomc DNA methylation and reduces gene expression in the hypothalamus. Despite this, we found that CRISPR-dCas9-TET1-mediated demethylation of Pomc was not sufficient to prevent abnormal weight gain following exposure to a high fat diet. Furthermore, CRISPR-dCas9-DNMT3a-mediated methylation of Pomc did not alter weight gain following exposure to standard or high fat diets. Collectively, these results suggest that high fat diet induced changes in Pomc DNA methylation are a consequence of, but do not directly contribute to, abnormal weight gain during the development of obesity. |
format | Online Article Text |
id | pubmed-10085038 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-100850382023-04-11 Controlling hypothalamic DNA methylation at the Pomc promoter does not regulate weight gain during the development of obesity McFadden, Taylor Gaito, Natasha Carucci, Isabella Fletchall, Everett Farrell, Kayla Jarome, Timothy J. PLoS One Research Article Obesity is a complex medical condition that is linked to various health complications such as infertility, stroke, and osteoarthritis. Understanding the neurobiology of obesity is crucial for responding to the etiology of this disease. The hypothalamus coordinates many integral activities such as hormone regulation and feed intake and numerous studies have observed altered hypothalamic gene regulation in obesity models. Previously, it was reported that the promoter region of the satiety gene, Pomc, has increased DNA methylation in the hypothalamus following short-term exposure to a high fat diet, suggesting that epigenetic-mediated repression of hypothalamic Pomc might contribute to the development of obesity. However, due to technical limitations, this has never been directly tested. Here, we used the CRISPR-dCas9-TET1 and dCas9-DNMT3a systems to test the role of Pomc DNA methylation in the hypothalamus in abnormal weight gain following acute exposure to a high fat diet in male rats. We found that exposure to a high fat diet increases Pomc DNA methylation and reduces gene expression in the hypothalamus. Despite this, we found that CRISPR-dCas9-TET1-mediated demethylation of Pomc was not sufficient to prevent abnormal weight gain following exposure to a high fat diet. Furthermore, CRISPR-dCas9-DNMT3a-mediated methylation of Pomc did not alter weight gain following exposure to standard or high fat diets. Collectively, these results suggest that high fat diet induced changes in Pomc DNA methylation are a consequence of, but do not directly contribute to, abnormal weight gain during the development of obesity. Public Library of Science 2023-04-10 /pmc/articles/PMC10085038/ /pubmed/37036864 http://dx.doi.org/10.1371/journal.pone.0284286 Text en © 2023 McFadden 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 McFadden, Taylor Gaito, Natasha Carucci, Isabella Fletchall, Everett Farrell, Kayla Jarome, Timothy J. Controlling hypothalamic DNA methylation at the Pomc promoter does not regulate weight gain during the development of obesity |
title | Controlling hypothalamic DNA methylation at the Pomc promoter does not regulate weight gain during the development of obesity |
title_full | Controlling hypothalamic DNA methylation at the Pomc promoter does not regulate weight gain during the development of obesity |
title_fullStr | Controlling hypothalamic DNA methylation at the Pomc promoter does not regulate weight gain during the development of obesity |
title_full_unstemmed | Controlling hypothalamic DNA methylation at the Pomc promoter does not regulate weight gain during the development of obesity |
title_short | Controlling hypothalamic DNA methylation at the Pomc promoter does not regulate weight gain during the development of obesity |
title_sort | controlling hypothalamic dna methylation at the pomc promoter does not regulate weight gain during the development of obesity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10085038/ https://www.ncbi.nlm.nih.gov/pubmed/37036864 http://dx.doi.org/10.1371/journal.pone.0284286 |
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