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Effect of excess weight and insulin resistance on DNA methylation in prepubertal children

Epigenetic mechanisms, such as DNA methylation, regulate gene expression and play a role in the development of insulin resistance. This study evaluates how the BMI z-score (BMIz) and the homeostatic model assessment of insulin resistance (HOMA-IR), alone or in combination, relate to clinical outcome...

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Autores principales: Barbosa, Pedro, Landes, Reid D., Graw, Stefan, Byrum, Stephanie D., Bennuri, Sirish, Delhey, Leanna, Randolph, Chris, MacLeod, Stewart, Reis, Andreia, Børsheim, Elisabet, Rose, Shannon, Carvalho, Eugenia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120504/
https://www.ncbi.nlm.nih.gov/pubmed/35589784
http://dx.doi.org/10.1038/s41598-022-12325-y
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author Barbosa, Pedro
Landes, Reid D.
Graw, Stefan
Byrum, Stephanie D.
Bennuri, Sirish
Delhey, Leanna
Randolph, Chris
MacLeod, Stewart
Reis, Andreia
Børsheim, Elisabet
Rose, Shannon
Carvalho, Eugenia
author_facet Barbosa, Pedro
Landes, Reid D.
Graw, Stefan
Byrum, Stephanie D.
Bennuri, Sirish
Delhey, Leanna
Randolph, Chris
MacLeod, Stewart
Reis, Andreia
Børsheim, Elisabet
Rose, Shannon
Carvalho, Eugenia
author_sort Barbosa, Pedro
collection PubMed
description Epigenetic mechanisms, such as DNA methylation, regulate gene expression and play a role in the development of insulin resistance. This study evaluates how the BMI z-score (BMIz) and the homeostatic model assessment of insulin resistance (HOMA-IR), alone or in combination, relate to clinical outcomes and DNA methylation patterns in prepubertal children. DNA methylation in peripheral blood mononuclear cells (PBMCs) and clinical outcomes were measured in a cohort of 41 prepubertal children. Children with higher HOMA-IR had higher blood pressure and plasma lactate levels while children with higher BMIz had higher triglycerides levels. Moreover, the DNA methylation analysis demonstrated that a 1 unit increase in the BMIz was associated with a 0.41 (95% CI: 0.29, 0.53) increase in methylation of a CpG near the PPP6R2 gene. This gene is important in the regulation of NF-kB expression. However, there was no strong evidence that the BMIz and the HOMA-IR were synergistically related to any clinical or DNA methylation outcomes. In summary, the results suggest that obesity and insulin resistance may impact metabolic health both independently in prepubertal children. In addition, obesity also has an impact on the DNA methylation of the PPP6R2 gene. This may be a novel underlying starting point for the systemic inflammation associated with obesity and insulin resistance, in this population.
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spelling pubmed-91205042022-05-21 Effect of excess weight and insulin resistance on DNA methylation in prepubertal children Barbosa, Pedro Landes, Reid D. Graw, Stefan Byrum, Stephanie D. Bennuri, Sirish Delhey, Leanna Randolph, Chris MacLeod, Stewart Reis, Andreia Børsheim, Elisabet Rose, Shannon Carvalho, Eugenia Sci Rep Article Epigenetic mechanisms, such as DNA methylation, regulate gene expression and play a role in the development of insulin resistance. This study evaluates how the BMI z-score (BMIz) and the homeostatic model assessment of insulin resistance (HOMA-IR), alone or in combination, relate to clinical outcomes and DNA methylation patterns in prepubertal children. DNA methylation in peripheral blood mononuclear cells (PBMCs) and clinical outcomes were measured in a cohort of 41 prepubertal children. Children with higher HOMA-IR had higher blood pressure and plasma lactate levels while children with higher BMIz had higher triglycerides levels. Moreover, the DNA methylation analysis demonstrated that a 1 unit increase in the BMIz was associated with a 0.41 (95% CI: 0.29, 0.53) increase in methylation of a CpG near the PPP6R2 gene. This gene is important in the regulation of NF-kB expression. However, there was no strong evidence that the BMIz and the HOMA-IR were synergistically related to any clinical or DNA methylation outcomes. In summary, the results suggest that obesity and insulin resistance may impact metabolic health both independently in prepubertal children. In addition, obesity also has an impact on the DNA methylation of the PPP6R2 gene. This may be a novel underlying starting point for the systemic inflammation associated with obesity and insulin resistance, in this population. Nature Publishing Group UK 2022-05-19 /pmc/articles/PMC9120504/ /pubmed/35589784 http://dx.doi.org/10.1038/s41598-022-12325-y 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Barbosa, Pedro
Landes, Reid D.
Graw, Stefan
Byrum, Stephanie D.
Bennuri, Sirish
Delhey, Leanna
Randolph, Chris
MacLeod, Stewart
Reis, Andreia
Børsheim, Elisabet
Rose, Shannon
Carvalho, Eugenia
Effect of excess weight and insulin resistance on DNA methylation in prepubertal children
title Effect of excess weight and insulin resistance on DNA methylation in prepubertal children
title_full Effect of excess weight and insulin resistance on DNA methylation in prepubertal children
title_fullStr Effect of excess weight and insulin resistance on DNA methylation in prepubertal children
title_full_unstemmed Effect of excess weight and insulin resistance on DNA methylation in prepubertal children
title_short Effect of excess weight and insulin resistance on DNA methylation in prepubertal children
title_sort effect of excess weight and insulin resistance on dna methylation in prepubertal children
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120504/
https://www.ncbi.nlm.nih.gov/pubmed/35589784
http://dx.doi.org/10.1038/s41598-022-12325-y
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