AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia

Background/Aims: Preeclampsia (PE) has long been assumed to be an ischemic disease of the placenta, although there is limited evidence as to how the ischemia impacts on the placenta. AMP-activated protein kinase (AMPK) is a key regulator of cellular energy metabolism and plays an important role in a...

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Main Authors: Xiaotao Yang, Ping Xu, Fumei Zhang, Li Zhang, Yangxi Zheng, Mingyu Hu, Lulu Wang, Ting-li Han, Chuan Peng, Lianlian Wang, Li Wen, Yiwen Zeng, Rufei Gao, Yong Xia, Chao Tong, Zhu Yang, Hongbo Qi, Philip N. Baker
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2018-08-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:https://www.karger.com/Article/FullText/492995
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spelling doaj-a222dcb253e445eea83e4047cff85d8e2020-11-25T00:53:35ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-08-0149257859410.1159/000492995492995AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in PreeclampsiaXiaotao YangPing XuFumei ZhangLi ZhangYangxi ZhengMingyu HuLulu WangTing-li HanChuan PengLianlian WangLi WenYiwen ZengRufei GaoYong XiaChao TongZhu YangHongbo QiPhilip N. BakerBackground/Aims: Preeclampsia (PE) has long been assumed to be an ischemic disease of the placenta, although there is limited evidence as to how the ischemia impacts on the placenta. AMP-activated protein kinase (AMPK) is a key regulator of cellular energy metabolism and plays an important role in a variety of ischemic diseases by enhancing energy production. The present study investigated placental metabolism in PE, and the role of AMPK in regulating trophoblast function. Methods: placentas from normal and PE complicated pregnancies were subjected to GC-MS to identify fatty acids (FA) metabolic fingerprints, and total FA oxidation was assessed by malondialdehyde (MDA) measurement. The AMPK-ACC signaling pathway was assessed by q-PCR and Western Blotting. HTR8/SVneo trophoblast cultures were exposed to different oxygenation conditions to establish an in vitro PE cell model; further analysis by GC-MS for metabolite profiling was then undertaken. Trophoblasts invasion was assessed by a matrigel transwell assay in the presence/absence of AMPK expression and after manipulations of AMPK activity, and then further validated by human villi outgrowth experiments. Results: AMPK phosphorylation and MDA production were significantly elevated in placentas from pregnancies complicated by PE. Metabolism of cis double bond FA was inhibited while trans double bond FA metabolism was promoted in PE placentas. HTR8/SVneo cell culture conditions of persistent low oxygenation mimicked the hyper-activation of AMPK and enhanced the FA oxidation that was observed in PE. AMPK activation impaired trophoblast invasion, while AMPK inhibition promoted trophoblast invasion. Conclusion: PE complicated placentas are associated with AMPK hyper-activation and consequent alterations in FA oxidation, which inhibit trophoblast invasion.https://www.karger.com/Article/FullText/492995PreeclampsiaAMPKPlacentaFatty acidsTrophoblastMetabolomics
collection DOAJ
language English
format Article
sources DOAJ
author Xiaotao Yang
Ping Xu
Fumei Zhang
Li Zhang
Yangxi Zheng
Mingyu Hu
Lulu Wang
Ting-li Han
Chuan Peng
Lianlian Wang
Li Wen
Yiwen Zeng
Rufei Gao
Yong Xia
Chao Tong
Zhu Yang
Hongbo Qi
Philip N. Baker
spellingShingle Xiaotao Yang
Ping Xu
Fumei Zhang
Li Zhang
Yangxi Zheng
Mingyu Hu
Lulu Wang
Ting-li Han
Chuan Peng
Lianlian Wang
Li Wen
Yiwen Zeng
Rufei Gao
Yong Xia
Chao Tong
Zhu Yang
Hongbo Qi
Philip N. Baker
AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia
Cellular Physiology and Biochemistry
Preeclampsia
AMPK
Placenta
Fatty acids
Trophoblast
Metabolomics
author_facet Xiaotao Yang
Ping Xu
Fumei Zhang
Li Zhang
Yangxi Zheng
Mingyu Hu
Lulu Wang
Ting-li Han
Chuan Peng
Lianlian Wang
Li Wen
Yiwen Zeng
Rufei Gao
Yong Xia
Chao Tong
Zhu Yang
Hongbo Qi
Philip N. Baker
author_sort Xiaotao Yang
title AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia
title_short AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia
title_full AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia
title_fullStr AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia
title_full_unstemmed AMPK Hyper-Activation Alters Fatty Acids Metabolism and Impairs Invasiveness of Trophoblasts in Preeclampsia
title_sort ampk hyper-activation alters fatty acids metabolism and impairs invasiveness of trophoblasts in preeclampsia
publisher Cell Physiol Biochem Press GmbH & Co KG
series Cellular Physiology and Biochemistry
issn 1015-8987
1421-9778
publishDate 2018-08-01
description Background/Aims: Preeclampsia (PE) has long been assumed to be an ischemic disease of the placenta, although there is limited evidence as to how the ischemia impacts on the placenta. AMP-activated protein kinase (AMPK) is a key regulator of cellular energy metabolism and plays an important role in a variety of ischemic diseases by enhancing energy production. The present study investigated placental metabolism in PE, and the role of AMPK in regulating trophoblast function. Methods: placentas from normal and PE complicated pregnancies were subjected to GC-MS to identify fatty acids (FA) metabolic fingerprints, and total FA oxidation was assessed by malondialdehyde (MDA) measurement. The AMPK-ACC signaling pathway was assessed by q-PCR and Western Blotting. HTR8/SVneo trophoblast cultures were exposed to different oxygenation conditions to establish an in vitro PE cell model; further analysis by GC-MS for metabolite profiling was then undertaken. Trophoblasts invasion was assessed by a matrigel transwell assay in the presence/absence of AMPK expression and after manipulations of AMPK activity, and then further validated by human villi outgrowth experiments. Results: AMPK phosphorylation and MDA production were significantly elevated in placentas from pregnancies complicated by PE. Metabolism of cis double bond FA was inhibited while trans double bond FA metabolism was promoted in PE placentas. HTR8/SVneo cell culture conditions of persistent low oxygenation mimicked the hyper-activation of AMPK and enhanced the FA oxidation that was observed in PE. AMPK activation impaired trophoblast invasion, while AMPK inhibition promoted trophoblast invasion. Conclusion: PE complicated placentas are associated with AMPK hyper-activation and consequent alterations in FA oxidation, which inhibit trophoblast invasion.
topic Preeclampsia
AMPK
Placenta
Fatty acids
Trophoblast
Metabolomics
url https://www.karger.com/Article/FullText/492995
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