title: Impaired fatty acid oxidation as a cause of liver disease associated with hyperemesis gravidarum.
abstract: Hyperemesis gravidarum (HG) is the most severe form of illness within the spectrum of nausea and vomiting of pregnancy. Liver disease, usually consisting of mild serum transaminase elevation, occurs in almost 50% of patients with HG. While multiple risk factors have been proposed, the etiology and underlying mechanism of maternal liver disease associated with HG remains unclear. In this report, we hypothesize that impairment of mitochondrial fatty acid oxidation (FAO) plays a role in the pathogenesis of maternal liver disease associated with HG. We hypothesize that women heterozygous for FAO defects develop HG associated with liver disease while carrying fetuses with FAO defects due to accumulation of fatty acids in placenta and subsequent generation of reactive oxygen species. Alternatively, it is possible that starvation leading to peripheral lipolysis and increased load of fatty acids in maternal-fetal circulation, combined with reduced capacity of the mitochondria to oxidize fatty acids in mothers heterozygous for FAO defects, can also cause HG and liver injury while carrying non-affected fetuses. The rationale for this hypothesis is discussed.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, University of Missouri, One Hospital Drive, Columbia, MO 65212, USA.
authors.forename: William M
authors.initials: WM
authors.lastname: Outlaw
authors.forename: Jamal A
authors.initials: JA
authors.lastname: Ibdah
mesh_terms: D019317:Evidence-Based Medicine; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D006939:Hyperemesis Gravidarum / Q000209:etiology* / Q000378:metabolism*; D008052:Lipid Metabolism, Inborn Errors / Q000150:complications* / Q000378:metabolism*; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010084:Oxidation-Reduction; D011247:Pregnancy
chemical_list: D005227:Fatty Acids