Metabolomics of a mouse model of preeclampsia induced by overexpressing soluble fms-like tyrosine kinase 1

Emiko Sato, Yukako Tsunokuni, Manami Kaneko, Daisuke Saigusa, Ritsumi Saito, Shuichi Shimma, Akiyo Sekimoto, Yoshiko Kawana, Yuji Oe, Sadayoshi Ito, Hiroshi Sato, Nobuyuki Takahashi

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Preeclampsia (PE) is a leading cause of maternal morbidity and mortality. Nicotinamide has beneficial effects on PE. In this study, we evaluated the effect of nicotinamide on placental development using a PE mouse model. To generate the PE model, a recombinant adenovirus to overproduce soluble fms-like tyrosine kinase 1 (sFlt-1) was administered to mice (Jcl:ICR) at 8.5 day post-coitum (dpc). Plasma and placenta samples were harvested at 12.5 dpc. Fetal and placental weight was significantly decreased at 12.5 dpc in PE mice. Plasma and placental acylcarnitine levels were significantly higher in PE mice than those in control mice. Glycolysis was accelerated and glucose metabolic flow was altered with hypoxia, leading to ATP shortage in the labyrinth of PE mice. In PE mice, ATP production was diminished, and fatty acid oxidation was accelerated in the placenta, consequently, blood carnitine and acylcarnitine levels were increased. The mitochondrial morphology in BeWo cells was impaired under hypoxia. Nicotinamide treatment reversed fetal growth restriction, placental development, and altered metabolic flow in the early stage in PE. In addition, nicotinamide normalized impaired mitochondrial morphology. Hence, targeting this metabolic alteration in the placenta using nicotinamide may serve as a potential therapeutic approach for PE treatment.

Original languageEnglish
Pages (from-to)1064-1071
Number of pages8
JournalBiochemical and biophysical research communications
Volume527
Issue number4
DOIs
Publication statusPublished - 2020 Jul 5

Keywords

  • Acetylcarnitine
  • Carnitine
  • Early-onset PE
  • Metabolomics
  • Nicotinamide
  • Preeclampsia

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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