线粒体功能障碍标志着母亲肥胖对MASLD的多代影响
Anneleen Heldens1,2, Milton Antwi1,2,3,4, Louis Onghena1,2,5
1Liver Research Center Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium.
JHEP reports : innovation in hepatology
|June 11, 2025
概括
孕产妇的西方饮食 (WD) 加剧了代谢功能障碍相关的脂肪性肝病 (MASLD) 在后代中,由线粒体功能障碍驱动. 治疗FGF21显示有望扭转这些影响.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 代谢疾病 代谢疾病
- 孕产妇和胎儿医学 孕产妇和胎儿医学
背景情况:
- 孕产妇的肥胖是后代患MASLD的危险因素,但潜在的机制尚不清楚.
- 母亲西方饮食 (WD) 对后代的多代影响 MASLD进展需要研究.
- 了解这些机制对于制定有针对性的干预措施至关重要.
研究的目的:
- 评估多代母性WD对男性后代MASLD进展的影响.
- 阐明潜在的机制,专注于线粒体功能障碍.
- 测试候选药物的治疗疗效,包括FGF21.
主要方法:
- 雌性小鼠在怀孕/哺乳期前和期间被食WD;后代被评估在不同的饮食和年龄.
- 在母体中进行肝胰岛素受体淘汰和血清生物标志物分析 (FGF21,MOTS-c).
- 在后代中评估了FGF21,赛马格卢提德和氨酸类型的治疗疗效.
主要成果:
- 孕产妇WD加重体重增加,胰岛素耐药性,肥胖症和奶后代的炎症.
- 纤维化和线粒体OXPHOS活性降低在暴露于母体WD的后代中观察到.
- FGF21治疗改善了脂肪肝炎和改善了线粒体功能.
结论:
- 孕产妇WD养加剧了男性后代的MASLD,线粒体功能障碍是主要的贡献者.
- 纤维化发展与母体WD暴露和后代线粒体功能障碍有关.
- FGF21激动体在逆转饮食诱导的MASLD和线粒体功能障碍方面显示出治疗潜力.
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