在生长受限制的胎儿中,肝脏葡萄糖产量增加,氧化代谢较低
Laura D Brown1, Paul J Rozance1, Dong Wang1
1Department of Pediatrics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
JCI insight
|April 30, 2024
概括
羊胎儿的胎儿生长限制 (FGR) 意外地显示肝氧化代谢减少,导致葡萄糖产量增加和潜在的2型糖尿病风险. 这一发现突显了FGR.的肝功能改变.
科学领域:
- 围产期编程是指围产期的编程
- 代谢障碍 代谢障碍 代谢障碍
- 肝脏新陈代谢 肝脏新陈代谢
背景情况:
- 胎儿生长限制 (FGR) 与早期肝糖生产 (HGP) 激活有关,这是2型糖尿病 (T2D) 的特征.
- 在FGR期间了解胎儿肝脏中的代谢适应对于预测产后健康风险至关重要.
研究的目的:
- 在FGR的羊模型中研究肝基质流和HGP.
- 测试假设FGR胎儿表现出肝脏乳酸和氨基酸吸收增加,以支持高HGP的假设.
主要方法:
- 直接测量HGP和基质流量使用胎儿肝脏导管在羊FGR模型.
- 分析肝脏代谢物丰富度,13C代谢物标记,酶活性和基因表达.
- 评估单独的肝细胞对于乳酸燃料的葡萄糖生产的能力,并测量肝脏的能量和氧化还原状态.
主要成果:
- 与对照组相比,FGR胎儿表现出增加的HGP和激活的葡萄糖基因.
- 意想不到的是,FGR肝脏显示了酸盐产量的增加,乳酸和葡萄糖原氨基酸吸收的减少,氧气消耗的降低.
- FGR肝脏组织显示氧化酸盐减少,乳酸盐生产增加,ATP降低,NADH/NAD+比率降低,孤立的肝细胞显示乳酸盐为燃料的葡萄糖产量增加.
结论:
- 在FGR胎儿中减少的肝氧化代谢可能会通过使碳可用,矛盾地增加HGP,同时也会导致营养和能量压力.
- 在FGR胎儿中肝脏HGP调节通路的内在编程可能会导致HGP升高和产后T2D风险增加.
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