Effect of excess weight and insulin resistance on DNA methylation in prepubertal children
Abstract 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 clinica...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-12325-y |
| _version_ | 1828323560039383040 |
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| author | Pedro Barbosa Reid D. Landes Stefan Graw Stephanie D. Byrum Sirish Bennuri Leanna Delhey Chris Randolph Stewart MacLeod Andreia Reis Elisabet Børsheim Shannon Rose Eugenia Carvalho |
| author_facet | Pedro Barbosa Reid D. Landes Stefan Graw Stephanie D. Byrum Sirish Bennuri Leanna Delhey Chris Randolph Stewart MacLeod Andreia Reis Elisabet Børsheim Shannon Rose Eugenia Carvalho |
| author_sort | Pedro Barbosa |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T18:54:19Z |
| format | Article |
| id | doaj.art-200dc9bbc04240b3977fd1b4e63e7df6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T18:54:19Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-200dc9bbc04240b3977fd1b4e63e7df62022-12-22T02:34:19ZengNature PortfolioScientific Reports2045-23222022-05-0112111010.1038/s41598-022-12325-yEffect of excess weight and insulin resistance on DNA methylation in prepubertal childrenPedro Barbosa0Reid D. Landes1Stefan Graw2Stephanie D. Byrum3Sirish Bennuri4Leanna Delhey5Chris Randolph6Stewart MacLeod7Andreia Reis8Elisabet Børsheim9Shannon Rose10Eugenia Carvalho11PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of CoimbraDepartment of Biostatistics, University of Arkansas for Medical SciencesDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical SciencesDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical SciencesArkansas Children’s Research InstituteArkansas Children’s Research InstituteArkansas Children’s Research InstituteArkansas Children’s Research InstituteDepartment of Medical Sciences (DCM), Institute for Research in Biomedicine (iBiMED), University of AveiroArkansas Children’s Research InstituteArkansas Children’s Research InstituteCenter for Neuroscience and Cell Biology, University of CoimbraAbstract 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.https://doi.org/10.1038/s41598-022-12325-y |
| spellingShingle | Pedro Barbosa Reid D. Landes Stefan Graw Stephanie D. Byrum Sirish Bennuri Leanna Delhey Chris Randolph Stewart MacLeod Andreia Reis Elisabet Børsheim Shannon Rose Eugenia Carvalho Effect of excess weight and insulin resistance on DNA methylation in prepubertal children Scientific Reports |
| 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 |
| url | https://doi.org/10.1038/s41598-022-12325-y |
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