3-Hydroxy Fatty Acid Induce Trophoblast and Hepatocyte Lipoapoptosis

Authors

Taylor Bruett, University of Nebraska LincolnFollow
Taylor Heng, University of Nebraska LincolnFollow
Sathish Kumar Natarajan, University of Nebraska - LincolnFollow

Date of this Version

Summer 8-2016

Document Type

Poster

Citation

University of Nebraska-Lincoln UCARE Poster Session, 2016

Comments

Copyright (c) 2016 Taylor Bruett, Taylor Heng, Sathish Kumar Natarajan

Abstract

Acute Fatty Liver of Pregnancy (AFLP) is a very rare and fatal condition for both the mother and the unborn offspring accompanied by severe maternal liver dysfunction. AFLP usually develops during the third trimester of pregnancy with symptoms of liver disease. AFLP is associated with a mutation in the enzyme, long-chain 3-hydroxy acyl CoA dehydrogenase (LCHAD) which is involved in the mitochondrial beta-oxidation of fatty acids. Defective beta-oxidation of fatty acids results in the individual unable to metabolize fatty acids which then causes fatty infiltration in their organs, such as the liver. This interferes with normal function of the liver and since fatty acids are an essential nutrient for mothers in the third trimester of pregnancy, an individual with this disease will not be able to survive long after child birth without the proper treatment. AFLP is an in-born error of metabolism and occurs in an autosomal recessive pattern, meaning it will take effect if an individual has both recessive alleles. This occurs when both the mother and father are heterozygous for the mutation in LCHAD and pass on their recessive alleles to the offspring.

The placenta acts as a lung, liver and kidney for the fetus and it also has the genetic make-up of the fetus. In AFLP, a fetus with homozygous mutation for LCHAD will have his/her placenta defective to metabolize the long chain fatty acids resulting in the accumulation of 3-hydroxyl fatty acids. Accumulated 3-hydroxyl fatty acids and other fatty acids enter the mother’s circulation and affects the maternal liver resulting in the complication of maternal liver disease observed in AFLP. The only form of treatment is for the mother to deliver the offspring, this will allow her to recover from maternal liver disease. As the liver accumulates with toxic 3-hydroxy fatty acids, it is not able to properly function. The hepatocytes, liver cells, are not able to maintain a proper balance between cell death and cells being produced. Cell death occurs at a higher rate than cells being replaced and results in liver dysfunction. Here our hypothesis is that the 3-hydroxy fatty acids that are released from the placenta induces hepatocyte lipoapoptosis, a metabolic programed cell death caused by the increased exposure of fatty acids.

This study will help clarify the mechanism of maternal liver damage that happens during AFLP. Our hypothesis will help identify the role of placental exosomes exacerbates hepatocyte lipoapoptosis due to the exposure of 3-hydroxy fatty acids.