Maternal high-fat diet alters Tet-mediated epigenetic regulation during heart development

被引:0
|
作者
Yang, Yuhan [1 ]
Rivera, Logan [1 ]
Fang, Shaohai [1 ]
Cavalier, Maryn [1 ]
Suris, Ashley [1 ]
Zhou, Yubin [2 ,3 ]
Huang, Yun [1 ,3 ]
机构
[1] Texas A&M Univ, Inst Biosci & Technol, Ctr Epigenet & Dis Prevent, Houston, TX 77030 USA
[2] Texas A&M Univ, Inst Biosci & Technol, Ctr Translat Canc Res, Houston, TX 77030 USA
[3] Texas A&M Univ, Sch Med, Dept Translat Med Sci, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
DNA DEMETHYLATION; LIPID-METABOLISM; 5-METHYLCYTOSINE;
D O I
10.1016/j.isci.2024.110631
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Imbalanced dietary intake, such as a high-fat diet (HFD) during pregnancy, has been associated with adverse offspring outcomes. Metabolic stress from imbalanced food intake alters the function of epigenetic regulators, resulting in abnormal transcriptional outputs in embryos to cause congenital disorders. We report herein that maternal HFD exposure causes metabolic changes in pregnant mice and non-compaction cardiomyopathy (NCC) in E15.5 embryos, accompanied by decreased 5-hydroxymethylcytosine (5hmC) levels and altered chromatin accessibility in embryonic heart tissues. Remarkably, maternal vitamin C supplementation mitigates these detrimental effects, likely by restoring iron, a cofactor for Tet enzymes, in a reduced state. Using a genetic approach, we further demonstrated that the cardioprotective benefits of vitamin C under HFD conditions are attributable to enhanced Tet activity. Our results highlight an interaction between maternal diet, specifically HFD or vitamin C, and epigenetic modifications during early heart development, emphasizing the importance of balanced maternal nutrition for healthy embryonic development.
引用
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页数:15
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