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. 2020 May;34(5):6508-6520. doi: 10.1096/fj.201902537R. Epub 2020 Mar 30.
This study aimed to evaluate the oxidative status and antioxidant capacity in maternal and fetal livers upon undernutrition as well as the connection between oxidative stress and lipid metabolism disorder. Ten ewes, who were pregnant for 115 days, were restricted to a 30% level of ad libitum feed intake to develop an undernourished model, while another 10 pregnant ewes were fed normally as controls. Undernutrition induced severe lipid metabolism disorder and oxidative stress in blood, maternal liver, and fetal liver. RNA-sequencing data displayed that antioxidant capacity was changed and antioxidant genes were downregulated in maternal and fetal livers of the undernourished model. Non-esterified fatty acids (NEFAs) and beta-hydroxybutyrate (BHBA) levels showed a positive correlation with oxidative indices and negative correlation with the expression of antioxidant genes both in maternal and fetal livers. Primary hepatocytes experiments confirmed that both high levels of NEFAs and BHBA could elicit oxidative stress and decrease antioxidant capacity, and the peroxisome proliferator-activated receptor alpha (PPARA)/retinoid X receptor alpha (RXRA) signaling pathway played a vital role in enhancing antioxidant capacity and relieving oxidative stress. In conclusion, maternal undernutrition induced lipid metabolism disorder, which downregulated antioxidant genes, decreased antioxidant activity, and further triggered oxidative stress both in maternal and fetal livers. Activation of PPARA/RXRA signaling could enhance antioxidant capacity and mitigate oxidative stress. Our findings contribute to protecting the pregnant mother and her fetus from oxidative stress.
本研究旨在评估营养不良时母胎肝脏的氧化状态和抗氧化能力，以及氧化应激与脂质代谢紊乱之间的关系。将 10 只怀孕 115 天的母羊限制其采食量至自由采食量的 30%，以建立营养不良模型，同时另选 10 只怀孕母羊正常饲养作为对照组。结果显示，营养不良导致母羊和胎羊血液、母肝和胎肝严重的脂质代谢紊乱和氧化应激。RNA-seq 数据显示，营养不良模型的母胎肝脏中抗氧化能力改变，抗氧化基因下调。母胎肝脏中的非酯化脂肪酸（NEFAs）和β-羟丁酸（BHBA）水平与氧化指标呈正相关，与抗氧化基因的表达呈负相关。原代肝细胞实验证实，高浓度的 NEFAs 和 BHBA 均可引起氧化应激，降低抗氧化能力，过氧化物酶体增殖物激活受体α（PPARA）/视黄酸 X 受体α（RXRA）信号通路在增强抗氧化能力和缓解氧化应激方面发挥重要作用。综上所述，母羊营养不良导致脂质代谢紊乱，下调抗氧化基因，降低抗氧化活性，进一步引发母胎肝脏的氧化应激。激活 PPARA/RXRA 信号通路可以增强抗氧化能力，减轻氧化应激。我们的研究结果有助于保护孕妇及其胎儿免受氧化应激的影响。
