TY - JOUR
T1 - Metabolomics of a mouse model of preeclampsia induced by overexpressing soluble fms-like tyrosine kinase 1
AU - Sato, Emiko
AU - Tsunokuni, Yukako
AU - Kaneko, Manami
AU - Saigusa, Daisuke
AU - Saito, Ritsumi
AU - Shimma, Shuichi
AU - Sekimoto, Akiyo
AU - Kawana, Yoshiko
AU - Oe, Yuji
AU - Ito, Sadayoshi
AU - Sato, Hiroshi
AU - Takahashi, Nobuyuki
N1 - Funding Information:
We acknowledge the technical assistance of the staff at the Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine. We thank Tomofumi Fushima and Reina Saijyo for their technical support. We acknowledge the Tohoku University Center for Gender Equality Promotion (TUMUG) Support Project for Research support staff. We would like to thank Editage (www.editage.jp) for English language editing. This study was supported by a Grant-In-Aid from the Japan Society for the Promotion of Society (no. 16K09599, 17K09682), Translational Research Network Program of Ministry of Education, Culture, Sports, Science and Technology of Japan (J140001192), the Naito Foundation, and Miyagi Kidney Foundation.
Funding Information:
We acknowledge the technical assistance of the staff at the Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine. We thank Tomofumi Fushima and Reina Saijyo for their technical support. We acknowledge the Tohoku University Center for Gender Equality Promotion (TUMUG) Support Project for Research support staff. We would like to thank Editage ( www.editage.jp ) for English language editing. This study was supported by a Grant-In-Aid from the Japan Society for the Promotion of Society (no. 16K09599 , 17K09682 ), Translational Research Network Program of Ministry of Education, Culture, Sports, Science and Technology of Japan ( J140001192 ), the Naito Foundation , and Miyagi Kidney Foundation .
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/7/5
Y1 - 2020/7/5
N2 - 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.
AB - 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.
KW - Acetylcarnitine
KW - Carnitine
KW - Early-onset PE
KW - Metabolomics
KW - Nicotinamide
KW - Preeclampsia
UR - http://www.scopus.com/inward/record.url?scp=85085014186&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85085014186&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2020.04.079
DO - 10.1016/j.bbrc.2020.04.079
M3 - Article
C2 - 32448504
AN - SCOPUS:85085014186
VL - 527
SP - 1064
EP - 1071
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -