MOE Joint International Research Laboratory of Animal Health & Food Safety , Nanjing Agricultural University , Nanjing 210095 , P. R. China.
Key Laboratory of Animal Physiology & Biochemistry , Nanjing Agricultural University , Nanjing 210095 , P. R. China.
J Agric Food Chem. 2018 Mar 21;66(11):2704-2713. doi: 10.1021/acs.jafc.7b05418. Epub 2018 Mar 8.
The growth-promoting action of betaine involves activation of GH/IGF-1 signaling, yet it remains unclear whether insulin-like growth factor 2 (IGF2), an imprinting gene, is affected by maternal dietary betaine supplementation. In this study, F1 offspring rats derived from dams fed basal or betaine-supplemented diet were examined at D21 and D63. Maternal betaine significantly upregulated the hepatic expression of IGF2 mRNA and protein in offspring rats at both D21 and D63, which was accompanied by enhanced hepatic IGF2 immunoreactivity and elevated serum IGF-2 level. Higher protein expression of betaine-homocysteine methyltransferase and DNA methyltransferase 1 was detected in the betaine group at D21, but not D63. However, hypermethylation of the imprinting control region of the IGF2/H19 locus at D21 was maintained at D63. These results indicate that maternal betaine modifies DNA methylation of IGF2/H19 imprinting control region in a mitotically stable fasion, which was associated with the activation hepatic IGF2 expression in offspring rats.
甜菜碱的促生长作用涉及激活 GH/IGF-1 信号通路，但目前尚不清楚胰岛素样生长因子 2（IGF2），一种印迹基因是否受母体膳食甜菜碱补充的影响。在这项研究中，在 D21 和 D63 时检查了来自用基础或甜菜碱补充饮食喂养的母体的 F1 后代大鼠。母体甜菜碱在 D21 和 D63 时均显著上调了后代大鼠肝脏中 IGF2 mRNA 和蛋白的表达，这伴随着肝 IGF2 免疫反应性增强和血清 IGF-2 水平升高。在 D21 时检测到甜菜碱组的甜菜碱同型半胱氨酸甲基转移酶和 DNA 甲基转移酶 1 的蛋白表达更高，但在 D63 时则没有。然而，在 D21 时 IGF2/H19 基因座印迹控制区的高甲基化在 D63 时仍得以维持。这些结果表明，母体甜菜碱以有丝分裂稳定的方式修饰 IGF2/H19 印迹控制区的 DNA 甲基化，这与后代大鼠肝脏中 IGF2 表达的激活有关。
