Maternal betaine supplementation affects fetal growth and lipid metabolism of high-fat fed mice in a temporal-specific manner.
Maternal betaine supplementation affects fetal growth and lipid metabolism of high-fat fed mice in a temporal-specific manner.
复制标题
DOI：
10.1038/s41387-018-0035-z
复制
发表时间：
2018-05-24
影响因子：
6.1
通讯作者：
Jiang X
中科院分区：
文献类型：
--
作者：
Joselit Y;Nanobashvili K;Jack-Roberts C;Greenwald E;Malysheva OV;Caudill MA;Saxena A;Jiang X
母亲肥胖增加妊娠期糖尿病（GDM）的风险，导致胎儿过度生长和后代长期代谢功能障碍。先前的研究表明，母体补充胆碱可以使肥胖小鼠的胎儿生长和后代肥胖正常化。本研究考察了补充甜菜碱（一种胆碱衍生物）是否对暴露于母亲肥胖和GDM的小鼠后代的胎儿代谢结果有积极影响。C57BL/6J小鼠分别饲喂高脂（HF）或对照（正常脂肪，NF）饮食，并在交配前4-6周和整个妊娠期间接受1%甜菜碱（BS）或对照未经处理（BC）的饮用水。收集母体、胎盘和胎儿样本进行代谢物和基因表达分析。在E12.5时，BS可抑制胎儿和胎盘的过度生长，下调HF、葡萄糖不耐受鼠胎盘中葡萄糖和脂肪酸转运蛋白（Glut1和Fatp1）以及促生长胰岛素样生长因子2 （Igf2）及其受体Igf1r （P < 0.05）。然而，这些影响在E17.5时消失。在E17.5时，与NF相比，BS减少了HF胎儿的肥胖，并阻止了肝脏甘油三酯的过度积累（P < 0.05）。BS胎儿肝脏微粒体甘油三酯转移蛋白（Mttp） mRNA表达增强（P < 0.01），促进VLDL合成和分泌。虽然我们之前报道过母体胆碱的补充下调了胎儿肝脏中参与新生脂肪生成的基因的mRNA表达，但在BS中没有观察到这种改变，这表明甜菜碱和胆碱对胎儿基因表达的不同影响。我们提出了母体BS在胎儿发育期间影响胎儿生长和HF小鼠脂质代谢结果的一种时间特异性机制。
Maternal obesity increases the risk of gestational diabetes mellitus (GDM), which results in fetal overgrowth and long-lasting metabolic dysfunctioning in the offspring. Previous studies show that maternal choline supplementation normalizes fetal growth and adiposity of progeny from obese mice. This study examines whether supplementation of betaine, a choline derivative, has positive effects on fetal metabolic outcomes in mouse progeny exposed to maternal obesity and GDM. C57BL/6J mice were fed either a high-fat (HF) diet or a control (normal-fat, NF) diet and received either 1% betaine (BS) or control untreated (BC) drinking water 4–6 weeks before timed-mating and throughout gestation. Maternal, placental, and fetal samples were collected for metabolite and gene-expression assays. At E12.5, BS prevented fetal and placental overgrowth and downregulated glucose and fatty acid transporters (Glut1 and Fatp1) and the growth-promoting insulin-like growth factor 2 (Igf2) and its receptor Igf1r in the placenta of HF, glucose-intolerant dams (P < 0.05). However, these effects disappeared at E17.5. At E17.5, BS reduced fetal adiposity and prevented liver triglyceride overaccumulation in HF versus NF fetuses (P < 0.05). BS fetal livers had enhanced mRNA expression of microsomal triglyceride transfer protein (Mttp) (P < 0.01), which promotes VLDL synthesis and secretion. Although we previously reported that maternal choline supplementation downregulated mRNA expression of genes involved in de novo lipogenesis in fetal livers, such alterations were not observed with BS, suggesting differential effects of betaine and choline on fetal gene expression. We propose a temporal-specific mechanism by which maternal BS influences fetal growth and lipid metabolic outcomes of HF mice during prenatal development.
登录
查看更多内容
影响因子：
2.5
作者：
Corbin KD;Zeisel SH
通讯作者：
Zeisel SH
DOI：
10.1016/j.bbrc.2014.12.005
发表时间：
2015-01-09
影响因子：
3.1
作者：
Lee, Icksoo
通讯作者：
Lee, Icksoo
影响因子：
5.5
作者：
Coan, P. M.;Vaughan, O. R.;Fowden, A. L.
通讯作者：
Fowden, A. L.
影响因子：
5.9
作者：
Jack-Roberts, Chauntelle;Joselit, Yaelle;Jiang, Xinyin
通讯作者：
Jiang, Xinyin
影响因子：
7.2
作者：
Ferrara, A;Kahn, HS;Hedderson, MM
通讯作者：
Hedderson, MM