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Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy

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
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA
Harry S. Truman Memorial Veterans Medical Center, Columbia, MO 65201, USA
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(1), 322;
Received: 1 January 2018 / Revised: 16 January 2018 / Accepted: 16 January 2018 / Published: 22 January 2018
(This article belongs to the Special Issue Hepatotoxicity: Molecular Mechanisms and Pathophysiology)
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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. View Full-Text
Keywords: acute fatty liver of pregnancy; 3-hydroxy fatty acids; lipoapoptosis; fatty acid oxidation acute fatty liver of pregnancy; 3-hydroxy fatty acids; lipoapoptosis; fatty acid oxidation

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Natarajan, S.K.; Ibdah, J.A. Role of 3-Hydroxy Fatty Acid-Induced Hepatic Lipotoxicity in Acute Fatty Liver of Pregnancy. Int. J. Mol. Sci. 2018, 19, 322.

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