Next Article in Journal
Heat Shock Proteins and Autophagy Pathways in Neuroprotection: From Molecular Bases to Pharmacological Interventions
Next Article in Special Issue
Interaction of Nevirapine with the Peptide Binding Groove of HLA-DRB1*01:01 and Its Effect on the Conformation of HLA-Peptide Complex
Previous Article in Journal
Identification of a Rare Germline Heterozygous Deletion Involving the Polycistronic miR-17–92 Cluster in Two First-Degree Relatives from a BRCA 1/2 Negative Chilean Family with Familial Breast Cancer: Possible Functional Implications
Previous Article in Special Issue
The Role of miRNAs in the Pathophysiology of Liver Diseases and Toxicity
Article Menu
Issue 1 (January) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2018, 19(1), 322; https://doi.org/10.3390/ijms19010322

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

1
Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583-0806, USA
2
Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65212, USA
3
Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, MO 65212, USA
4
Harry S. Truman Memorial Veterans Medical Center, Columbia, MO 65201, USA
*
Author to whom correspondence should be addressed.
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)
Full-Text   |   PDF [1609 KB, uploaded 23 January 2018]   |  

Abstract

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
Figures

Graphical abstract

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).
SciFeed

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top