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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...

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Autores principales: Chen, Yan-Ting, Hu, Yun, Yang, Qi-Yuan, Son, Jun Seok, Liu, Xiang-Dong, de Avila, Jeanene M., Zhu, Mei-Jun, Du, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2020
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.
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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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