Regulation of fetal liver transcription by maternal nutritional stress. Regulation of fetal liver transcription by maternal nutritional stress

Pregnancy is a time of extreme metabolic demand that requires coordinated adaptations between mother and fetus. To determine the contributions of maternal and fetal metabolism to metabolic plasticity during gestation, mice with a liver-specific Carnitine Palmitoyltransferase-2 knockout mice (Cpt2-/-), or Pparα KO mice were subjected to late-gestation nutrient stress, a 24hr fast from E16.5 to E17.5. The fetal response to maternal fasting was dominated by maternal lipid metabolism as the loss of maternal hepatic fatty acid oxidation or Pparα signaling accelerated fetal liver transcriptional programing. These data show that maternal nutritional environment is a major driver of perinatal metabolic programing and plasticity. Overall design: Examination of wild-type and Ppara KO E17.5 fetal liver following a 24hr fast in WT, Cpt2-/-, and Ppara KO dams, with 4 biological replicates each.

妊娠是一段代谢需求极高的时期，需母体与胎儿之间实现协同适应性调控。为明确妊娠期间母体与胎儿代谢对代谢可塑性的贡献，研究人员对肝特异性肉碱棕榈酰转移酶2（Carnitine Palmitoyltransferase-2, CPT2）敲除小鼠（Cpt2-/-）或过氧化物酶体增殖物激活受体α（Pparα）敲除小鼠，于妊娠晚期施加营养应激处理——即从妊娠第16.5天（E16.5）至妊娠第17.5天（E17.5）实施24小时禁食。母体禁食引发的胎儿反应以母体脂质代谢为主导：母体肝脏脂肪酸氧化功能缺失或Pparα信号通路受损，可加速胎儿肝脏的转录编程过程。本研究数据表明，母体营养环境是围产期代谢编程与代谢可塑性的核心驱动因素。总体实验设计：在野生型（WT）、Cpt2-/-及Pparα KO孕鼠接受24小时禁食后，对其胎龄E17.5的野生型与Pparα KO胎儿肝脏进行检测，每组设置4个生物学重复。