Laboratory of Gastrointestinal Microbiology, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
National Center for International Research on Animal Gut Nutrition, National Experimental Teaching Demonstration Center of Animal Science, Nanjing Agricultural University, Nanjing, China.
FASEB J. 2019 Sep;33(9):9990-10004. doi: 10.1096/fj.201900406R. Epub 2019 Jun 5.
Undernutrition accelerates body fat mobilization to alleviate negative energy balance, which disrupts homeostasis of lipid metabolism in maternal liver. However, little is known about its effect on fetal metabolism and development. Here, a sheep model was used to explore whether maternal undernutrition induces fetal lipid metabolism disorder and further inhibits fetal hepatic development. Twenty pregnant ewes were either fed normally or restricted to 30% level for 15 d, after which fetal hepatic samples were collected to conduct transcriptome, metabolome, histomorphology, and biochemical analysis. Results showed that maternal undernutrition altered the general transcriptome profile and metabolic mode in fetal liver. Fatty acid oxidation and ketogenesis were enhanced in fetal livers of undernourished ewes, which might be promoted by the activated peroxisome proliferator-activated receptor α signaling pathway, whereas cholesterol, steroid, and fatty acid synthesis were repressed. Maternal undernutrition increased triglyceride synthesis, decreased triglyceride degradation, and inhibited phospholipid degradation and synthesis in fetal liver. In addition, our data revealed that maternal undernutrition extremely inhibited DNA replication, cell cycle progression, and antiapoptosis and broke the balance between cell proliferation and apoptosis in fetal liver, indicating that maternal undernutrition affects the growth and development of fetal liver. Generally, these findings provide evidence that maternal undernutrition during pregnancy disturbs fetal lipid metabolism and inhibits fetal hepatic development in sheep, which greatly contribute to the further study of fetal metabolism and development in human beings.-Xue, Y., Guo, C., Hu, F., Zhu, W., Mao, S. Maternal undernutrition induces fetal hepatic lipid metabolism disorder and affects the development of fetal liver in a sheep model.
营养不良会加速身体脂肪动员，以减轻负氮平衡，从而破坏母肝脂质代谢的内稳态。然而，其对胎儿代谢和发育的影响知之甚少。在这里，我们使用绵羊模型来探讨母体营养不良是否会导致胎儿脂质代谢紊乱，并进一步抑制胎儿肝脏发育。将 20 只怀孕母羊正常喂养或限制喂养 15 天，30%的水平，之后收集胎儿肝脏样本进行转录组、代谢组、组织形态学和生化分析。结果表明，母体营养不良改变了胎儿肝脏的一般转录组谱和代谢模式。在营养不良母羊的胎儿肝脏中，脂肪酸氧化和酮体生成增强，这可能是由激活的过氧化物酶体增殖物激活受体α信号通路促进的，而胆固醇、类固醇和脂肪酸合成则受到抑制。母体营养不良增加了胎儿肝脏中甘油三酯的合成，减少了甘油三酯的降解，抑制了磷脂的降解和合成。此外，我们的数据还表明，母体营养不良严重抑制了胎儿肝脏中 DNA 复制、细胞周期进程和抗凋亡，打破了细胞增殖和凋亡之间的平衡，表明母体营养不良影响胎儿肝脏的生长和发育。总的来说，这些发现为母体在怀孕期间营养不良会扰乱胎儿脂质代谢并抑制绵羊胎儿肝脏发育提供了证据，这对进一步研究人类胎儿代谢和发育有很大帮助。
