Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy.
Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy.
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DOI：
10.3390/ijms19010322
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发表时间：
2018-01-22
影响因子：
5.6
通讯作者：
Ibdah JA
中科院分区：
文献类型：
--
作者：
Natarajan SK;Ibdah JA
妊娠期急性脂肪肝（Acute fatty liver of pregnancy，AFLP）是一种对母亲和未出生的后代都具有灾难性影响的疾病，发生在妊娠的最后三个月，具有显著的孕产妇和围产儿死亡率。AFLP也被认为是产科和医疗紧急情况。母体AFLP与编码线粒体长链羟酰辅酶A脱氢酶（LCHAD）的基因中的胎儿纯合突变（1528 G>C）高度相关。LCHAD的突变导致3-羟基脂肪酸如3-羟基肉豆蔻酸、3-羟基棕榈酸和3-羟基二羧酸在胎盘中的积累，然后将其分流到母体循环中，导致在AFLP患者中观察到的急性肝损伤的发展。在这篇综述中，我们将讨论增加3-羟基脂肪酸在引起肝脏脂毒性和诱导氧化应激，线粒体功能障碍和肝细胞脂凋亡的机制作用。此外，我们还审查了3-羟基脂肪酸在LCHAD缺乏症患者中引起胎盘损伤、胰岛β细胞糖脂毒性、脑损伤和视网膜上皮细胞脂凋亡中的作用。
Acute fatty liver of pregnancy (AFLP), a catastrophic illness for both the mother and the unborn offspring, develops in the last trimester of pregnancy with significant maternal and perinatal mortality. AFLP is also recognized as an obstetric and medical emergency. Maternal AFLP is highly associated with a fetal homozygous mutation (1528G>C) in the gene that encodes for mitochondrial long-chain hydroxy acyl-CoA dehydrogenase (LCHAD). The mutation in LCHAD results in the accumulation of 3-hydroxy fatty acids, such as 3-hydroxy myristic acid, 3-hydroxy palmitic acid and 3-hydroxy dicarboxylic acid in the placenta, which are then shunted to the maternal circulation leading to the development of acute liver injury observed in patients with AFLP. In this review, we will discuss the mechanistic role of increased 3-hydroxy fatty acid in causing lipotoxicity to the liver and in inducing oxidative stress, mitochondrial dysfunction and hepatocyte lipoapoptosis. Further, we also review the role of 3-hydroxy fatty acids in causing placental damage, pancreatic islet β-cell glucolipotoxicity, brain damage, and retinal epithelial cells lipoapoptosis in patients with LCHAD deficiency.
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影响因子：
25.7
作者：
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DOI：
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发表时间：
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期刊：
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1996-06-01
期刊：
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