TY - JOUR
T1 - Role of 3-hydroxy fatty acid-induced hepatic lipotoxicity in acute fatty liver of pregnancy
AU - Natarajan, Sathish Kumar
AU - Ibdah, Jamal A.
N1 - Funding Information:
Acknowledgments: We thank Justin L. Mott and Carol Casey for their helpful discussions. The work described was supported in part by grants from National Institutes of Health (DK-56345 and DK-68210 to Jamal A. Ibdah), Nebraska Center for Prevention of Obesity Disease, National Institute of General Medical Sciences (P20GM104320 to Sathish Kumar Natarajan), the Nebraska Agricultural Experiment station with funding from the Hatch Act (Accession Number 1014526 to Sathish Kumar Natarajan) through the United States Department of Agriculture (USDA) National Institute of Food and Agriculture, and the University of Nebraska-Lincoln. The contents of this manuscript are solely the responsibility of the authors.
Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2018/1/22
Y1 - 2018/1/22
N2 - 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.
AB - 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.
KW - 3-hydroxy fatty acids
KW - Acute fatty liver of pregnancy
KW - Fatty acid oxidation
KW - Lipoapoptosis
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U2 - 10.3390/ijms19010322
DO - 10.3390/ijms19010322
M3 - Review article
C2 - 29361796
AN - SCOPUS:85040953736
SN - 1661-6596
VL - 19
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 1
M1 - 322
ER -