Hepatic Insulin Signaling Changes: Possible Mechanism in Prenatal Hypoxia-Increased Susceptibility of Fatty Liver in Adulthood
Hepatic Insulin Signaling Changes: Possible Mechanism in Prenatal Hypoxia-Increased Susceptibility of Fatty Liver in Adulthood
复制标题
肝脏胰岛素信号变化：产前缺氧导致成年期脂肪肝易感性增加的可能机制
DOI：
10.1210/en.2012-1349
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发表时间：
2012-10-01
期刊：
影响因子：
4.8
通讯作者：
Xu, Zhice
中科院分区：
文献类型：
--
作者：
Cao, Li;Mao, Caiping;Xu, Zhice
非酒精性脂肪肝（NAFLD）与胰岛素抵抗密切相关。产前缺氧（PH）是一个危险因素，在编程的胰岛素抵抗，葡萄糖耐受不良，代谢功能障碍，在以后的生活，虽然机制尚不清楚。在这项研究中，代谢和组织学变化以及肝脏胰岛素信号传导机制的作用，确定在增加NAFLD的易感性在胎儿和后代暴露于PH。妊娠大鼠暴露于缺氧（O-2 10%）在怀孕期间表现出胎儿体重和肝脏重量以及肝脏体重比下降，而这些变化没有观察到的后代。然而，雄性肝脏体重比增加后，PH应激。显微镜分析表明，暴露于PH导致胎仔和后代肝实质细胞结构扭曲，细胞结构减少。胎儿的血糖和胰岛素水平较低，胰岛素敏感性增强，肝脏胰岛素信号元件表达增加。此外，胰岛素抵抗，受损的葡萄糖稳态，并改变表达的胰岛素信号元件发生在后代。出生后缺氧增加了肝脏中的肝脂滴和甘油三酯，而胰岛素信号元件的表达在暴露于PH的后代中较少，除了葡萄糖转运蛋白2。结果表明，PH可能通过影响胰岛素信号通路（包括葡萄糖转运蛋白2），导致后代肝细胞异型增生和代谢变化，从而增强NAFLD的易感性。（内分泌学153：4955-4965，2012）
Nonalcoholic fatty liver disease (NAFLD) is strongly linked to insulin resistance. Prenatal hypoxia (PH) is a risk factor in programming of insulin resistance, glucose intolerance, and metabolic dysfunctions in later life, although the mechanisms are unclear. In this study, the role of metabolic and histological changes as well as the hepatic insulin signaling mechanisms were determined in increasing susceptibility of NAFLD in the fetus and offspring exposed to PH. Pregnant rats exposed to hypoxia (O-2 10%) during pregnancy demonstrated decreased fetal body and liver weight as well as liver to body weight ratio, whereas these changes were not observed in the offspring. However, male liver to body weight ratio increased after PH stress. Microscopic analysis demonstrated that exposure to PH resulted in distorted architecture of the hepatic parenchyma cells with reduced cellularity in the fetus and offspring. Blood glucose and insulin levels were lower with enhanced insulin sensitivity and increased expression of hepatic insulin-signaling elements in the fetus. Furthermore, insulin resistance, impaired glucose homeostasis, and altered expression of insulin-signaling elements occurred in the offspring. Postnatal hypoxia increased hepatic lipid droplets and triglyceride in liver, whereas expressions of insulin-signaling elements were less in the offspring exposed to PH except glucose transporters 2. The results indicated that PH contributed to hepatocyte heteroplasia and metabolic changes that enhanced vulnerability for NAFLD in the offspring, probably via affecting insulin signaling pathway, including glucose transporters 2. (Endocrinology 153: 4955-4965, 2012)