title: Apolipoprotein E4 allele is associated with substantial changes in the plasma lipids and hyaluronic acid content in patients with nonalcoholic fatty liver disease.
abstract: Fat may affect progression of liver damage in patients with non-alcoholic fatty liver disease (NAFLD). In this study we characterize the state of lipid metabolism in 22 patients with NAFLD and different Apo-E variants. Total concentration of plasma total fatty acids was quantified by gas chromatography, while their derivatives by liquid chromatography/tandem mass spectrometry (LC ESI MS/MS). The ratio of plasma saturated fatty acid to monounsaturated fatty acid increased, whereas the ratio of polyunsaturated fatty acids to saturated fatty acids was reduced in Apo-E4 carriers. Simultaneously, the levels of individual plasma linoleic, arachidonic, and alpha linolenic acids significantly increased in subjects with the Apo-E4 allele. The 15-lipoxygenase metabolite, 13-hydroxyoctadecadienoic acid, was significantly higher in Apo-E3 carriers (p<0.006). 5-oxo-6,8,11,14-eicosatetraenoic acid was significantly elevated in Apo-E4 carriers (p<0.009). A significant difference in hyaluronic acid concentration (p<0.0016) as well as predicted advanced fibrosis (using the BARD scoring system) was found in Apo-E4 carriers (p<0.01). We suggest that a distinct mechanism of fibrosis between Apo E alleles. In Apo-E4 carriers, an elevation in 5-oxo-6,8,11,14-eicosatetraenoic acid synthesis and fatty acid dysfunction may induce fibrosis, while an inflammatory process may be the main cause of fibrosis in Apo-E3 carriers.
authors.affiliation: Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Szczecin, Poland. ewast@sci.pum.edu.pl.
authors.forename: E
authors.initials: E
authors.lastname: Stachowska
authors.forename: D
authors.initials: D
authors.lastname: Maciejewska
authors.forename: P
authors.initials: P
authors.lastname: Ossowski
authors.forename: A
authors.initials: A
authors.lastname: Drozd
authors.forename: K
authors.initials: K
authors.lastname: Ryterska
authors.forename: M
authors.initials: M
authors.lastname: Banaszczak
authors.forename: M
authors.initials: M
authors.lastname: Milkiewicz
authors.forename: J
authors.initials: J
authors.lastname: Raszeja-Wyszomirska
authors.forename: M
authors.initials: M
authors.lastname: Slebioda
authors.forename: P
authors.initials: P
authors.lastname: Milkiewicz
authors.forename: H
authors.initials: H
authors.lastname: Jelen
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D001095:Arachidonic Acids / Q000097:blood; D005227:Fatty Acids / Q000097:blood*; D005234:Fatty Liver / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood*; D008041:Linoleic Acids / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease
chemical_list: D053327:Apolipoprotein E4; D001095:Arachidonic Acids; D005227:Fatty Acids; D008041:Linoleic Acids; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; C024348:13-hydroxy-9,11-octadecadienoic acid; D006820:Hyaluronic Acid