MOE Joint International Research Laboratory of Animal Health & Food Safety, Nanjing Agricultural University, 210095, Nanjing, P. R. China.
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, 210095, Nanjing, P. R. China.
Endocrine. 2019 Jun;64(3):544-551. doi: 10.1007/s12020-019-01906-z. Epub 2019 Mar 28.
Betaine contains three methyl groups and plays a critical role in regulating glucose and lipid metabolism via epigenetic modifications. However, it is unclear whether prenatal betaine intake could affect cholesterol metabolism of progeny through DNA methylation.
Hence, pregnant rats were randomly divided into control and betaine groups fed standard diet or 1% betaine supplementation diet, respectively, throughout gestation and lactation.
Maternal betaine exposure significantly (P < 0.05) increased serum and hepatic cholesterol contents but not triglyceride levels in offspring rats. Accordantly, maternal intake of betaine markedly downregulated (P < 0.05) hepatic cholesterol 7 alpha-hydroxylase (CYP7A1) expression at both the mRNA and protein level, while the protein content of low-density lipoprotein receptor (LDLR) was upregulated in the liver of betaine-exposed rats. In addition, prenatal betaine supplementation extremely increased (P < 0.05) hepatic betaine-homocysteine methyltransferase (BHMT) expression at the mRNA and protein level but not affected the expression of other key enzymes involved in methionine metabolism. Furthermore, hepatic hypermethylation of CYP7A1 gene promoter was observed in progeny rats derived from betaine-supplemented dams.
Our results provide evidence that maternal betaine supplementation significantly enhances hepatic cholesterol contents accompanied with alterations of cholesterol metabolic genes and hypermethylation in offspring rats at weaning.
甜菜碱含有三个甲基，通过表观遗传修饰在调节葡萄糖和脂质代谢中发挥关键作用。然而，尚不清楚产前甜菜碱摄入是否可以通过 DNA 甲基化影响后代的胆固醇代谢。
因此，将怀孕大鼠随机分为对照组和甜菜碱组，分别在整个妊娠和哺乳期给予标准饮食或 1%甜菜碱补充饮食。
母体甜菜碱暴露显著（P < 0.05）增加了后代大鼠血清和肝脏中的胆固醇含量，但不增加甘油三酯水平。相应地，母体甜菜碱摄入明显下调了（P < 0.05）肝脏胆固醇 7α-羟化酶（CYP7A1）在 mRNA 和蛋白水平上的表达，而低密脂蛋白受体（LDLR）的蛋白含量在甜菜碱暴露的大鼠肝脏中上调。此外，产前甜菜碱补充剂极显著增加（P < 0.05）肝脏甜菜碱-同型半胱氨酸甲基转移酶（BHMT）在 mRNA 和蛋白水平上的表达，但不影响其他参与蛋氨酸代谢的关键酶的表达。此外，在断奶后代大鼠的肝脏中观察到 CYP7A1 基因启动子的高度甲基化。
我们的结果提供了证据，表明母体甜菜碱补充剂显著增加了肝脏胆固醇含量，同时改变了胆固醇代谢基因和后代大鼠在断奶时的高甲基化。
