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Early-life stress perturbs the epigenetics of Cd36 concurrent with adult onset of NAFLD in mice
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in the U.S. and worldwide. The roles of early postnatal life stress (EPLS) and the fatty acid translocase (CD36) on the pathogenesis of adult-onset NAFLD remain unknown. We hypothesized that EPLS, in the f...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10665193/ https://www.ncbi.nlm.nih.gov/pubmed/37479748 http://dx.doi.org/10.1038/s41390-023-02714-y |
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author | Fu, Qi Frick, Jenna M. O’Neil, Maura F. Eller, Olivia C. Morris, E. Matthew Thyfault, John P. Christianson, Julie A. Lane, Robert H. |
author_facet | Fu, Qi Frick, Jenna M. O’Neil, Maura F. Eller, Olivia C. Morris, E. Matthew Thyfault, John P. Christianson, Julie A. Lane, Robert H. |
author_sort | Fu, Qi |
collection | PubMed |
description | BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in the U.S. and worldwide. The roles of early postnatal life stress (EPLS) and the fatty acid translocase (CD36) on the pathogenesis of adult-onset NAFLD remain unknown. We hypothesized that EPLS, in the form of neonatal maternal separation (NMS), would predispose mice towards developing adult NAFLD, increase hepatic CD36 expression, and differentially methylate Cd36 promoter concurrently. METHODS: NMS was performed on mice from postnatal day 1 to 21 and a high-fat/high-sucrose (HFS) diet was started at 4 weeks of age to generate four experimental groups: Naive-control diet (CD), Naive-HFS, NMS-CD, and NMS-HFS. RESULTS: NMS alone caused NAFLD in adult male mice at 25 weeks of age. The effects of NMS and HFS were generally additive in terms of NAFLD, hepatic Cd36 mRNA levels, and hepatic Cd36 promoter DNA hypomethylation. Cd36 promoter methylation negatively correlated with Cd36 mRNA levels. Two differentially methylated regions (DMRs) within Cd36 promoter regions appeared to be vulnerable to NMS in the mouse. CONCLUSIONS: Our findings suggest that NMS increases the risk of an individual, particularly male, towards NAFLD when faced with a HFS diet later in life. IMPACT: The key message of this article is that neonatal maternal separation and a postweaning high-fat/high-sucrose diet increased the risk of an individual, particularly male, towards NAFLD in adult life. What this study adds to the existing literature includes the identification of two vulnerable differentially methylated regions in hepatic Cd36 promoters whose methylation levels very strongly negatively correlated with Cd36 mRNA. The impact of this article is that it provides an early-life environment-responsive gene/promoter methylation model and an animal model for furthering the mechanistic study on how the insults in early-life environment are “transmitted” into adulthood and caused NAFLD. |
format | Online Article Text |
id | pubmed-10665193 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-106651932023-07-21 Early-life stress perturbs the epigenetics of Cd36 concurrent with adult onset of NAFLD in mice Fu, Qi Frick, Jenna M. O’Neil, Maura F. Eller, Olivia C. Morris, E. Matthew Thyfault, John P. Christianson, Julie A. Lane, Robert H. Pediatr Res Basic Science Article BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in the U.S. and worldwide. The roles of early postnatal life stress (EPLS) and the fatty acid translocase (CD36) on the pathogenesis of adult-onset NAFLD remain unknown. We hypothesized that EPLS, in the form of neonatal maternal separation (NMS), would predispose mice towards developing adult NAFLD, increase hepatic CD36 expression, and differentially methylate Cd36 promoter concurrently. METHODS: NMS was performed on mice from postnatal day 1 to 21 and a high-fat/high-sucrose (HFS) diet was started at 4 weeks of age to generate four experimental groups: Naive-control diet (CD), Naive-HFS, NMS-CD, and NMS-HFS. RESULTS: NMS alone caused NAFLD in adult male mice at 25 weeks of age. The effects of NMS and HFS were generally additive in terms of NAFLD, hepatic Cd36 mRNA levels, and hepatic Cd36 promoter DNA hypomethylation. Cd36 promoter methylation negatively correlated with Cd36 mRNA levels. Two differentially methylated regions (DMRs) within Cd36 promoter regions appeared to be vulnerable to NMS in the mouse. CONCLUSIONS: Our findings suggest that NMS increases the risk of an individual, particularly male, towards NAFLD when faced with a HFS diet later in life. IMPACT: The key message of this article is that neonatal maternal separation and a postweaning high-fat/high-sucrose diet increased the risk of an individual, particularly male, towards NAFLD in adult life. What this study adds to the existing literature includes the identification of two vulnerable differentially methylated regions in hepatic Cd36 promoters whose methylation levels very strongly negatively correlated with Cd36 mRNA. The impact of this article is that it provides an early-life environment-responsive gene/promoter methylation model and an animal model for furthering the mechanistic study on how the insults in early-life environment are “transmitted” into adulthood and caused NAFLD. Nature Publishing Group US 2023-07-21 2023 /pmc/articles/PMC10665193/ /pubmed/37479748 http://dx.doi.org/10.1038/s41390-023-02714-y Text en © The Author(s) 2023 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 | Basic Science Article Fu, Qi Frick, Jenna M. O’Neil, Maura F. Eller, Olivia C. Morris, E. Matthew Thyfault, John P. Christianson, Julie A. Lane, Robert H. Early-life stress perturbs the epigenetics of Cd36 concurrent with adult onset of NAFLD in mice |
title | Early-life stress perturbs the epigenetics of Cd36 concurrent with adult onset of NAFLD in mice |
title_full | Early-life stress perturbs the epigenetics of Cd36 concurrent with adult onset of NAFLD in mice |
title_fullStr | Early-life stress perturbs the epigenetics of Cd36 concurrent with adult onset of NAFLD in mice |
title_full_unstemmed | Early-life stress perturbs the epigenetics of Cd36 concurrent with adult onset of NAFLD in mice |
title_short | Early-life stress perturbs the epigenetics of Cd36 concurrent with adult onset of NAFLD in mice |
title_sort | early-life stress perturbs the epigenetics of cd36 concurrent with adult onset of nafld in mice |
topic | Basic Science Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10665193/ https://www.ncbi.nlm.nih.gov/pubmed/37479748 http://dx.doi.org/10.1038/s41390-023-02714-y |
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