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Gestational palmitic acid suppresses embryonic GATA-binding protein 4 signaling and causes congenital heart disease

Cell Rep Med. 2023-02; 
Rui Zhao, Li Cao, Wen-Jun Gu, Lei Li, Zhong-Zhong Chen, Jie Xiang, Ze-Yu Zhou, Bo Xu, Wei-Dong Zang, Xiang-Yu Zhou, Jing Cao, Kun Sun, Jian-Yuan Zhao
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摘要

Dysregulated maternal fatty acid metabolism increases the risk of congenital heart disease (CHD) in offspring with an unknown mechanism, and the effect of folic acid fortification in preventing CHD is controversial. Using gas chromatography coupled to either a flame ionization detector or mass spectrometer (GC-FID/MS) analysis, we find that the palmitic acid (PA) concentration increases significantly in serum samples of pregnant women bearing children with CHD. Feeding pregnant mice with PA increased CHD risk in offspring and cannot be rescued by folic acid supplementation. We further find that PA promotes methionyl-tRNA synthetase (MARS) expression and protein lysine homocysteinylation (K-Hcy) of GATA4 and res... More

关键词

GATA4, congenital heart disease, maternal fatty acids, methionyl-tRNA synthetase, palmitic acid, protein lysine homocysteinylation