Gestational palmitic acid suppresses embryonic GATA-binding protein 4 signaling and causes congenital heart disease
Gestational palmitic acid suppresses embryonic GATA-binding protein 4 signaling and causes congenital heart disease
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DOI：
10.1016/j.xcrm.2023.100953
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Jian-Yuan Zhao
中科院分区：
文献类型：
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作者：
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
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 results in GATA4 inhibition and abnormal heart development. Targeting K-Hcy modification by either genetic ablation of Mars or using N-acetyl-L-cysteine (NAC) decreases CHD onset in high-PA-diet-fed mice. In summary, our work links maternal malnutrition and MARS/K-Hcy with the onset of CHD and provides a potential strategy in preventing CHD by targeting K-Hcy other than folic acid supplementation.
