气候变化领域集成服务门户(CCPortal): Embryonic exposure to hyper glucocorticoids suppresses brown fat development and thermogenesis via REDD1

CCPortal

DOI	10.1016/j.scib.2020.10.015
	Embryonic exposure to hyper glucocorticoids suppresses brown fat development and thermogenesis via REDD1
	Chen Y.-T.; Hu Y.; Yang Q.-Y.; Liu X.-D.; Son J.S.; de Avila J.M.; Zhu M.-J.; Du M.
发表日期	2021
ISSN	20959273
起始页码	478
结束页码	489
卷号	66 期号:5
英文摘要	Maternal stress during pregnancy is prevailing worldwide, which exposes fetuses to intrauterine hyper glucocorticoids (GC), programming offspring to obesity and metabolic diseases. Despite the importance of brown adipose tissue (BAT) in maintaining long-term metabolic health, impacts of prenatal hyper GC on postnatal BAT thermogenesis and underlying regulations remain poorly defined. Pregnant mice were administrated with synthetic GC dexamethasone (DEX) at levels comparable to fetal GC exposure of stressed mothers. Prenatal GC exposure dose-dependently reduced BAT thermogenic activity, contributing to lower body temperature and higher mortality of neonates; such difference was abolished under thermoneutrality, underscoring BAT deficiency was the major contributor to adverse changes in postnatal thermogenesis due to excessive GC. Prenatal GC exposure highly activated Redd1 expression and reduced Ppargc1a transcription from the alternative promoter (Ppargc1a-AP) in neonatal BAT. During brown adipocyte differentiation, ectopic Redd1 expression reduced Ppargc1a-AP expression and mitochondrial biogenesis; and the inhibitory effects of GC on mitochondrial biogenesis and Ppargc1a-AP expression were blocked by Redd1 ablation. Redd1 reduced protein kinase A phosphorylation and suppressed cyclic adenosine monophosphate (cAMP) -responsive element-binding protein (CREB) binding to the cAMP regulatory element (CRE) in Ppargc1a-AP promoter, leading to Ppargc1a-AP inactivation. In summary, excessive maternal GC exposure during pregnancy dysregulates Redd1-Ppargc1a-AP axis, which impairs fetal BAT development, hampering postnatal thermogenic adaptation and metabolic health of offspring. © 2020 Science China Press
关键词	Brown fat Fetus Glucocorticoids Maternal stress Mitochondrial biogenesis REDD1
英文关键词	Biosynthesis; Hormones; Mammals; Mitochondria; Obstetrics; Plants (botany); Proteins; Adipocyte differentiation; Cyclic adenosine monophosphate (cAMP); Element-binding proteins; Inhibitory effect; Metabolic disease; Mitochondrial biogenesis; Regulatory elements; Thermogenic activity; Metabolism
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207368
作者单位	Nutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA 99164, United States; School of Food Sciences, Washington State University, Pullman, WA 99164, United States
推荐引用方式 GB/T 7714	Chen Y.-T.,Hu Y.,Yang Q.-Y.,et al. Embryonic exposure to hyper glucocorticoids suppresses brown fat development and thermogenesis via REDD1[J],2021,66(5).
APA	Chen Y.-T..,Hu Y..,Yang Q.-Y..,Liu X.-D..,Son J.S..,...&Du M..(2021).Embryonic exposure to hyper glucocorticoids suppresses brown fat development and thermogenesis via REDD1.Science Bulletin,66(5).
MLA	Chen Y.-T.,et al."Embryonic exposure to hyper glucocorticoids suppresses brown fat development and thermogenesis via REDD1".Science Bulletin 66.5(2021).