肥胖怀孕期间母亲的肝脏适应包括叶子特异性线粒体变化和氧化应激
Luís F Grilo1,2, João D Martins1, Mariana S Diniz1
1CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, UC-Biotech, Biocant Park, Cantanhede, Portugal.
Clinical science (London, England : 1979)
|August 11, 2023
概括
怀孕期间的孕产妇肥胖会改变肝脏代谢,增加氧化应激,影响线粒体功能. 这些变化使母亲容易患有与怀孕相关的肝脏疾病,强调肥胖是显著的危险因素.
科学领域:
- 产科和妇科 产科和妇科
- 肝病学 肝病学是一种肝病学.
- 孕产妇和胎儿医学 孕产妇和胎儿医学
背景情况:
- 孕产妇肥胖 (MO) 是一个日益严重的全球性问题,影响了近一半的怀孕.
- 妊娠相关性肝病 (PALD) 影响约3%的怀孕,通常涉及母亲的肝氧化应激和线粒体功能障碍.
- 孕产妇肝病对母亲和胎儿都有风险,强调需要了解MO的作用.
研究的目的:
- 在怀孕晚期孕产妇肥胖的背景下,研究 mitochondria 和氧化应激中的特定肝脏代谢变化.
- 阐明在怀孕期间将孕产妇肥胖与肝脏疾病联系在一起的病理生理机制.
主要方法:
- 从对照和MO绵羊中采集了母性肝组织,怀孕期为90%.
- 分析包括氧化还原状态,线粒体呼吸链 (MRC) 活性和蛋白质表达,氧化应激标志物和代谢重塑指标.
- 研究的特定标记是复杂的I-IV活性,ATP合成酶,ANT-1/2,VDAC,PKA活性,NAD+/NADH比,脂质过氧化,GSH/GSSG比,以及抗氧化酶活性/表达.
主要成果:
- 孕产妇的肥胖导致MRC复合II活性下降,并改变了其子单元 (SDHA,SDHB) 的表达.
- 尽管mtCO1表达减少,但观察到MRC复合物-I和复合物-IV的活性增加,同时增加ATP合成酶子单元 (ATP5A).
- 肝脏氧化还原状态的显著变化,包括增加的氧化应激,脂质过氧化,以及改变的GSH/GSSG比率. 抗氧化酶活动和蛋白质表达减少,而GPX-1丰度增加.
结论:
- 孕产妇的肥胖导致肝脏显著的代谢重塑,其特点是线粒体功能障碍和与氧化应激相一致的改变的氧化还原状态.
- 这些MO诱导的肝脏变化是PALD的标志,支持MO作为怀孕期间肝脏疾病的关键风险因素.
- 这些发现强调氧化应激和线粒体功能障碍是导致肥胖孕妇患肝病倾向的关键机制.
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