Prenatal betaine exposure modulates hypothalamic expression of cholesterol metabolic genes in cockerels through modifications of DNA methylation
Prenatal betaine exposure modulates hypothalamic expression of cholesterol metabolic genes in cockerels through modifications of DNA methylation
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DOI：
10.3382/ps/pew437
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发表时间：
2017-06-01
期刊：
影响因子：
4.4
通讯作者：
Zhao, Ruqian
中科院分区：
文献类型：
--
作者：
Idriss, Abdulrahman A.;Hu, Yun;Zhao, Ruqian
胆固醇对神经元发育和大脑功能是必不可少的。在此之前，我们曾报道甜菜碱对鸡肝脏胆固醇代谢有调节作用，但目前尚不清楚母体甜菜碱是否影响鸡下丘脑的胆固醇含量和胆固醇代谢基因的表达。本试验用生理盐水或甜菜碱按2.5 mg/枚的剂量注射鸡蛋，在相同的条件下饲养，直到日龄。母体甜菜碱显著增加日龄公鸡的体重和抑制攻击行为，并显著上调下丘脑5-HTR1a受体的表达(P<；0.05)。同时，鸡蛋中甜菜碱显著增加(P<；0.05)下丘脑总胆固醇和胆固醇酯的含量，这与显著上调(P<；0.05)下丘脑胆固醇生物合成基因的表达一致，如固醇调节元件结合蛋白2和3-羟基-3-甲基戊二酰辅酶A还原酶以及乙酰辅酶A胆固醇酰基转移酶1，该酶将游离胆固醇转化为胆固醇酯以供储存。相比之下，介导胆固醇摄取的低密度脂蛋白受体显著下调(P<；0.05)。在体外，甜菜碱可显著增强甜菜碱-同型半胱氨酸甲基转移酶和DNA甲基转移酶1的表达(P<；0.05)，这与修饰的胆固醇代谢基因启动子上CpG甲基化的改变有关。这些结果表明，母体甜菜碱通过改变胆固醇代谢基因启动子上的DNA甲基化来调节公鸡下丘脑的胆固醇代谢。
Cholesterol is essential for neuronal development and brain function. Previously we reported that in ovo administration of betaine modulates hepatic cholesterol metabolism in the chicken, yet it remains unknown whether maternal betaine affects the cholesterol content and the expression of cholesterol metabolic genes in chicken hypothalamus. In this study, eggs were injected with saline or betaine at 2.5 mg/egg, and the hatchlings were raised under the same condition until 64 d of age. Maternal betaine significantly (P = 0.05) increased the body weight and suppressed aggressive behavior of 64-day-old cockerels, in association with significantly (P < 0.05) up-regulated expression of 5-HTR1A receptor in the hypothalamus. Concurrently, betaine in ovo significantly increased (P < 0.05) the hypothalamic content of total cholesterol and cholesterol ester, which coincided with significantly up-regulated (P < 0.05) hypothalamic expression of cholesterol biosynthetic genes, such as sterol-regulatory element binding protein 2 and 3-hydroxy-3-methylglutaryl-CoA reductase as well as acetyl-CoA cholesterol acyltransferase 1, which converts free cholesterol to cholesterol ester for storage. In contrast, low density lipoprotein receptor, which mediates the cholesterol uptake, was significantly down-regulated (P < 0.05). In ovo betaine administration significantly enhanced the expression of betaine-homocysteine methyltransferase and DNA methyltransferase 1 (P < 0.05), which was associated with alterations of CpG methylation on the promoter of modified cholesterol metabolic genes. These results indicate that maternal betaine modulates hypothalamic cholesterol metabolism in cockerels through modifying DNA methylation on the promoter of cholesterol metabolic genes.