Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583-0806, USA.
Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, USA.
Int J Mol Sci. 2018 Jan 22;19(1):322. doi: 10.3390/ijms19010322.
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.
妊娠急性脂肪肝（AFLP）是一种灾难性的疾病，对母亲和未出生的胎儿都有影响，通常发生在妊娠晚期，母体和围产儿死亡率都很高。AFLP 也被认为是一种产科和医学急症。母体 AFLP 与编码线粒体长链羟酰基辅酶 A 脱氢酶（LCHAD）的基因的纯合子突变（1528G>C）密切相关。LCHAD 中的突变导致 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）在胎盘内蓄积，然后转移到母体循环中，导致 AFLP 患者观察到的急性肝损伤。在这篇综述中，我们将讨论增加的 3-羟基脂肪酸在引起肝脂肪毒性和诱导氧化应激、线粒体功能障碍和肝细胞脂肪凋亡中的作用机制。此外，我们还回顾了 3-羟基脂肪酸在引起 LCHAD 缺乏症患者的胎盘损伤、胰岛β细胞糖脂毒性、脑损伤和视网膜上皮细胞脂肪凋亡中的作用。
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