Fetal betaine exposure modulates hypothalamic expression of cholesterol metabolic genes in offspring cockerels with modification of promoter DNA methylation.
Fetal betaine exposure modulates hypothalamic expression of cholesterol metabolic genes in offspring cockerels with modification of promoter DNA methylation.
复制标题
胎儿甜菜碱暴露通过启动子 DNA 甲基化调节子代公鸡胆固醇代谢基因下丘脑的表达
DOI：
10.1016/j.psj.2019.12.040
复制
发表时间：
2020-05
期刊：
影响因子：
4.4
通讯作者：
Zhao R
中科院分区：
文献类型：
--
作者：
Idriss AA;Hu Y;Sun Q;Hou Z;Yang S;Omer NA;Abobaker H;Zhao R
在文献中，母体甜菜碱调节鸡孵化后的下丘脑胆固醇代谢，但目前尚不清楚这种影响是否可以代代相传。在本研究中，卵注射生理盐水或甜菜碱2.5mg/卵，并在相同的条件下饲养孵化的幼鱼（F1），直到性成熟。对照组和甜菜碱组都使用人工授精从他们的公鸡收集精子。受精卵孵化，下一代（F2）的孵化，提高到64 D的年龄。甜菜碱组F2代公鸡体重显著降低（P < 0.05），下丘脑总胆固醇和胆固醇酯含量显著降低（P < 0.05）。与此一致，下丘脑胆固醇生物合成基因SREBP 2和HMGCR的表达显著下调（P < 0.05），胆固醇转化相关和排泄相关基因CYP 46 A1和ABCA 1的表达也显著下调（P < 0.05）。这些变化与调节性神经肽（包括脑源性神经营养因子、神经肽Y和促肾上腺皮质激素释放激素）mRNA表达的显著下调相一致。此外，还修饰了参与甲基转移循环的基因。甜菜碱同型半胱氨酸甲基转移酶表达下调（P < 0.05），DNA甲基转移酶1表达上调（P = 0.06）。S-腺苷蛋氨酸/S-腺苷同型半胱氨酸的比例较高，在下丘脑的甜菜碱处理的F2公鸡，这是与显着修改的CpG甲基化对这些受影响的基因的启动子。这些结果表明，甜菜碱可能通过改变F2代公鸡基因启动子区DNA甲基化水平来调节中枢胆固醇代谢和下丘脑脑功能相关基因的表达。
In documents, maternal betaine modulates hypothalamic cholesterol metabolism in chicken posthatchings, but it remains unclear whether this effect can be passed on by generations. In present study, eggs were injected with saline or betaine at 2.5 mg/egg, and the hatchlings (F1) were raised under the same condition until sexual maturation. Both the control group and the betaine group used artificial insemination to collect sperm from their cockerels. Fertilized eggs were incubated, and the hatchlings of the following generation (F2) were raised up to 64 D of age. F2 cockerels in betaine group showed significantly (P < 0.05) lower body weight, which was associated with significantly decreased (P < 0.05) hypothalamic content of total cholesterol and cholesterol ester. Concordantly, hypothalamic expression of cholesterol biosynthetic genes, SREBP2 and HMGCR, were significantly downregulated (P < 0.05), together with cholesterol conversion-related and excretion-related genes, CYP46A1 and ABCA1. These changes coincided with a significant downregulation in mRNA expression of regulatory neuropeptides including brain-derived neurotrophic factor, neuropeptide Y, and corticotropin-releasing hormone. Moreover, genes involved in methyl transfer cycle were also modified. Betaine homocysteine methyltransferase (P < 0.05) was downregulated, yet DNA methyltransferase1 tended to be upregulated (P = 0.06). S-adenosyl methionine/S-adenosylhomocysteine ratio was higher in the hypothalamus of betaine-treated F2 cockerels, which was associated with significantly modified CpG methylation on the promoter of those affected genes. These results suggested that betaine might regulate central cholesterol metabolism and hypothalamic expression of genes related to brain function by altering promoter DNA methylation in F2 cockerels.
登录
查看更多内容
影响因子：
4.2
作者：
Almeida, Maria R.;Macario, Maria C.;Santana, Isabel
通讯作者：
Santana, Isabel
影响因子：
4.8
作者：
Fukui, Kenji;Ferris, Heather A.;Kahn, C. Ronald
通讯作者：
Kahn, C. Ronald
DOI：
10.1096/fj.15-280800
发表时间：
2016-04
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Aiken CE;Tarry-Adkins JL;Penfold NC;Dearden L;Ozanne SE
通讯作者：
Ozanne SE
影响因子：
2.8
作者：
Catherine NL;Gonzalez A;Boyle M;Sheehan D;Jack SM;Hougham KA;McCandless L;MacMillan HL;Waddell C;British Columbia Healthy Connections Project Scientific Team
通讯作者：
British Columbia Healthy Connections Project Scientific Team
影响因子：
4.4
作者：
Idriss, Abdulrahman A.;Hu, Yun;Zhao, Ruqian
通讯作者：
Zhao, Ruqian