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Excessive Glucocorticoids During Pregnancy Impair Fetal Brown Fat Development and Predispose Offspring to Metabolic Dysfunctions
Maternal stress during pregnancy exposes fetuses to hyperglucocorticoids, which increases the risk of metabolic dysfunctions in offspring. Despite being a key tissue for maintaining metabolic health, the impacts of maternal excessive glucocorticoids (GC) on fetal brown adipose tissue (BAT) developme...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372078/ https://www.ncbi.nlm.nih.gov/pubmed/32409491 http://dx.doi.org/10.2337/db20-0009 |
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author | Chen, Yan-Ting Hu, Yun Yang, Qi-Yuan Son, Jun Seok Liu, Xiang-Dong de Avila, Jeanene M. Zhu, Mei-Jun Du, Min |
author_facet | Chen, Yan-Ting Hu, Yun Yang, Qi-Yuan Son, Jun Seok Liu, Xiang-Dong de Avila, Jeanene M. Zhu, Mei-Jun Du, Min |
author_sort | Chen, Yan-Ting |
collection | PubMed |
description | Maternal stress during pregnancy exposes fetuses to hyperglucocorticoids, which increases the risk of metabolic dysfunctions in offspring. Despite being a key tissue for maintaining metabolic health, the impacts of maternal excessive glucocorticoids (GC) on fetal brown adipose tissue (BAT) development and its long-term thermogenesis and energy expenditure remain unexamined. For testing, pregnant mice were administered dexamethasone (DEX), a synthetic GC, in the last trimester of gestation, when BAT development is the most active. DEX offspring had glucose, insulin resistance, and adiposity and also displayed cold sensitivity following cold exposure. In BAT of DEX offspring, Ppargc1a expression was suppressed, together with reduced mitochondrial density, and the brown progenitor cells sorted from offspring BAT demonstrated attenuated brown adipogenic capacity. Increased DNA methylation in Ppargc1a promoter had a fetal origin; elevated DNA methylation was also detected in neonatal BAT and brown progenitors. Mechanistically, fetal GC exposure increased GC receptor/DNMT3b complex in binding to the Ppargc1a promoter, potentially driving its de novo DNA methylation and transcriptional silencing, which impaired fetal BAT development. In summary, maternal GC exposure during pregnancy increases DNA methylation in the Ppargc1a promoter, which epigenetically impairs BAT thermogenesis and energy expenditure, predisposing offspring to metabolic dysfunctions. |
format | Online Article Text |
id | pubmed-7372078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-73720782021-08-01 Excessive Glucocorticoids During Pregnancy Impair Fetal Brown Fat Development and Predispose Offspring to Metabolic Dysfunctions Chen, Yan-Ting Hu, Yun Yang, Qi-Yuan Son, Jun Seok Liu, Xiang-Dong de Avila, Jeanene M. Zhu, Mei-Jun Du, Min Diabetes Obesity Studies Maternal stress during pregnancy exposes fetuses to hyperglucocorticoids, which increases the risk of metabolic dysfunctions in offspring. Despite being a key tissue for maintaining metabolic health, the impacts of maternal excessive glucocorticoids (GC) on fetal brown adipose tissue (BAT) development and its long-term thermogenesis and energy expenditure remain unexamined. For testing, pregnant mice were administered dexamethasone (DEX), a synthetic GC, in the last trimester of gestation, when BAT development is the most active. DEX offspring had glucose, insulin resistance, and adiposity and also displayed cold sensitivity following cold exposure. In BAT of DEX offspring, Ppargc1a expression was suppressed, together with reduced mitochondrial density, and the brown progenitor cells sorted from offspring BAT demonstrated attenuated brown adipogenic capacity. Increased DNA methylation in Ppargc1a promoter had a fetal origin; elevated DNA methylation was also detected in neonatal BAT and brown progenitors. Mechanistically, fetal GC exposure increased GC receptor/DNMT3b complex in binding to the Ppargc1a promoter, potentially driving its de novo DNA methylation and transcriptional silencing, which impaired fetal BAT development. In summary, maternal GC exposure during pregnancy increases DNA methylation in the Ppargc1a promoter, which epigenetically impairs BAT thermogenesis and energy expenditure, predisposing offspring to metabolic dysfunctions. American Diabetes Association 2020-08 2020-05-14 /pmc/articles/PMC7372078/ /pubmed/32409491 http://dx.doi.org/10.2337/db20-0009 Text en © 2020 by the American Diabetes Association https://www.diabetesjournals.org/content/licenseReaders may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license. |
spellingShingle | Obesity Studies Chen, Yan-Ting Hu, Yun Yang, Qi-Yuan Son, Jun Seok Liu, Xiang-Dong de Avila, Jeanene M. Zhu, Mei-Jun Du, Min Excessive Glucocorticoids During Pregnancy Impair Fetal Brown Fat Development and Predispose Offspring to Metabolic Dysfunctions |
title | Excessive Glucocorticoids During Pregnancy Impair Fetal Brown Fat Development and Predispose Offspring to Metabolic Dysfunctions |
title_full | Excessive Glucocorticoids During Pregnancy Impair Fetal Brown Fat Development and Predispose Offspring to Metabolic Dysfunctions |
title_fullStr | Excessive Glucocorticoids During Pregnancy Impair Fetal Brown Fat Development and Predispose Offspring to Metabolic Dysfunctions |
title_full_unstemmed | Excessive Glucocorticoids During Pregnancy Impair Fetal Brown Fat Development and Predispose Offspring to Metabolic Dysfunctions |
title_short | Excessive Glucocorticoids During Pregnancy Impair Fetal Brown Fat Development and Predispose Offspring to Metabolic Dysfunctions |
title_sort | excessive glucocorticoids during pregnancy impair fetal brown fat development and predispose offspring to metabolic dysfunctions |
topic | Obesity Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372078/ https://www.ncbi.nlm.nih.gov/pubmed/32409491 http://dx.doi.org/10.2337/db20-0009 |
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