Maternal obesity in sheep impairs foetal hepatic mitochondrial respiratory chain capacity.
Maternal obesity in sheep impairs foetal hepatic mitochondrial respiratory chain capacity.
复制标题
绵羊母体肥胖会损害胎儿肝线粒体呼吸链的能力。
DOI：
10.1111/eci.13375
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发表时间：
2021
影响因子：
5.5
通讯作者：
Oliveira,PauloJ
中科院分区：
文献类型：
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作者：
Serafim,TeresaL;Cunha-Oliveira,Teresa;Deus,ClaudiaM;Sardão,VilmaA;Cardoso,InesM;Yang,Shanshan;Odhiambo,JohnF;Ghnenis,AdelB;Smith,AshleyM;Li,Junfei;Nathanielsz,PeterW;Ford,StephenP;Oliveira,PauloJ
背景母亲肥胖（MO）引起的子宫内营养环境的变化导致胎儿代谢功能障碍，使后代易患晚年代谢疾病。由于线粒体在肝脏代谢和功能中起着至关重要的作用，我们假设，MO在怀孕前和整个怀孕方案胎羊肝脏线粒体phenotype.Material and methodsEwes吃致肥胖饮食（150%的要求; MO），或100%的要求（CTR），从60天前的概念。在妊娠0.9时取出胎肝。我们测量胎肝线粒体DNA拷贝数，超氧化物歧化酶，组织蛋白酶B和D和选定的蛋白质含量，总磷脂和心磷脂和线粒体呼吸链complex.ResultsA的线粒体复合物I，II-III和IV，但不乌头酸酶的活动显着减少，在MO观察。在抗氧化机制中，总超氧化物歧化酶（SOD）和SOD 2的活性在MO中有显着增加。然而，未发现自噬相关蛋白含量（p62、beclin-I、LC 3-I、LC 3-II和Lamp 2A）以及组织蛋白酶B和D活性存在差异。在MO.ConclusionsThe数据表明，MO损害胎肝线粒体的氧化能力，影响线粒体总磷脂含量减少21.5%。此外，MO影响胎肝氧化还原途径的调节，表明代谢适应更高的胎儿脂质环境。胎儿肝脏代谢在子宫内编程的后果可能会持续存在，并在以后的生活中损害线粒体生物能量学，并增加对代谢性疾病的易感性。
BackgroundChanges in the nutritional environment in utero induced by maternal obesity (MO) lead to foetal metabolic dysfunction predisposing offspring to later‐life metabolic diseases. Since mitochondria play a crucial role in hepatic metabolism and function, we hypothesized that MO prior to conception and throughout pregnancy programmes foetal sheep liver mitochondrial phenotype.Material and methodsEwes ate an obesogenic diet (150% requirements; MO), or 100% requirements (CTR), from 60 days prior to conception. Foetal livers were removed at 0.9 gestation. We measured foetal liver mitochondrial DNA copy number, activity of superoxide dismutase, cathepsins B and D and selected protein content, total phospholipids and cardiolipin and activity of mitochondrial respiratory chain complexes.ResultsA significant decrease in activities of mitochondrial complexes I, II‐III and IV, but not aconitase, was observed in MO. In the antioxidant machinery, there was a significant increase in activity of total superoxide dismutase (SOD) and SOD2 in MO. However, no differences were found regarding autophagy‐related protein content (p62, beclin‐I, LC3‐I, LC3‐II and Lamp2A) and cathepsin B and D activities. A 21.5% decrease in total mitochondrial phospholipid was observed in MO.ConclusionsThe data indicate that MO impairs foetal hepatic mitochondrial oxidative capacity and affects total mitochondrial phospholipid content. In addition, MO affects the regulation of foetal liver redox pathways, indicating metabolic adaptations to the higher foetal lipid environment. Consequences of in utero programming of foetal hepatic metabolism may persist and compromise mitochondrial bioenergetics in later life, and increase susceptibility to metabolic diseases.