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Review
. 2011 Sep;4(3):99-103.
doi: 10.1258/om.2011.100071. Epub 2011 Jul 4.

Acute fatty liver of pregnancy: an update on mechanisms

Sathish Kumar Natarajan  1 , Kavitha R Thangaraj  1 , Ashish Goel  1 , C E Eapen  1 , K A Balasubramanian  1 , Anup Ramachandran  1
Affiliations
Review

Acute fatty liver of pregnancy: an update on mechanisms

Sathish Kumar Natarajan et al. Obstet Med. 2011 Sep.

Abstract

Acute fatty liver of pregnancy (AFLP), characterized by hepatic microvesicular steatosis, is a sudden catastrophic illness occurring almost exclusively in the third trimester of pregnancy. Defective fatty acid oxidation in the fetus has been shown to be associated with this disease. Since the placenta has the same genetic makeup as the fetus and as AFLP patients generally recover following delivery, we hypothesized that the placenta might be involved in pathogenesis of this disease. In an animal model of hepatic microvesicular steatosis (using sodium valproate), we found that microvesicular steatosis results in mitochondrial structural alterations and oxidative stress in subcellular organelles of the liver. In placentas from patients with AFLP, we observed placental mitochondrial dysfunction and oxidative stress in subcellular organelles. In addition, defective placental fatty acid oxidation results in accumulation of toxic mediators such as arachidonic acid. Escape of these mediators into the maternal circulation might affect the maternal liver resulting in microvesicular steatosis.

Keywords: complications; hepatology; maternal mortality; maternal–fetal medicine; metabolism.

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Figures

Figure 1
Figure 1
Classical β-oxidation pathway in the mitochondria. Fatty acids (FAs) are activated to form fatty acyl CoA by the acyl CoA synthatase present in the outer mitochondrial membrane. To import FA into mitochondrial matrix, fatty acyl carnitine is formed by carnitine acyl transferase I and the carnitine translocase helps in transporting it into the mitochondrial matrix. Carnitine acyl transferase II converts fatty acyl carnitine back to fatty acyl CoA. β-Oxidation starts with the action of acyl-CoA dehydrogenase activity. The mitochondrial trifunctional protein, which consists of enoly CoA hydratase, hydroxyl acyl CoA dehydrogenase and thiolase activities leads to the formation of an acyl CoA molecule with two carbons less and acetyl CoA as products
Figure 2
Figure 2
Role of placental mitochondrial dysfunction and oxidative stress in the maternal liver injury. Defective fatty acid oxidation in the placenta results in accumulation of fatty acid (FA) in the placenta. Increased FA is directed to peroxisomal ω-oxidation resulting increased free radicals production. Release of free radicals, FA and its metabolites into circulation might damage maternal liver leading to microvesicular steatosis
See this image and copyright information in PMC

References

    1. Ibdah JA. Acute fatty liver of pregnancy: an update on pathogenesis and clinical implications. World J Gastroenterol 2006;12:7397–404 - PMC - PubMed
    1. Schoeman MN, Batey RG, Wilcken B. Recurrent acute fatty liver of pregnancy associated with a fatty-acid oxidation defect in the offspring. Gastroenterology 1991;100:544–8 - PubMed
    1. Eskelin PM, Laitinen KA, Tyni TA. Elevated hydroxyacylcarnitines in a carrier of LCHAD deficiency during acute liver disease of pregnancy – a common feature of the pregnancy complication? Mol Genet Metab 2010;100:204–6 - PubMed
    1. Diderholm B, Stridsberg M, Ewald U, Lindeberg-Norden S, Gustafsson J. Increased lipolysis in non-obese pregnant women studied in the third trimester. BJOG 2005;112:713–8 - PubMed
    1. Haggarty P. Fatty acid supply to the human fetus. Annu Rev Nutr 2010;30:237–55 - PubMed

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