title: Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa.
abstract: Individuals with anorexia nervosa (AN) restrict eating and become emaciated. They tend to have an aversion to foods rich in fat. Because epoxide hydrolase 2 (EPHX2) was identified as a novel AN susceptibility gene, and because its protein product, soluble epoxide hydrolase (sEH), converts bioactive epoxides of polyunsaturated fatty acid (PUFA) to the corresponding diols, lipidomic and metabolomic targets of EPHX2 were assessed to evaluate the biological functions of EPHX2 and their role in AN. Epoxide substrates of sEH and associated oxylipins were measured in ill AN, recovered AN and gender- and race-matched controls. PUFA and oxylipin markers were tested as potential biomarkers for AN. Oxylipin ratios were calculated as proxy markers of in vivo sEH activity. Several free- and total PUFAs were associated with AN diagnosis and with AN recovery. AN displayed elevated n-3 PUFAs and may differ from controls in PUFA elongation and desaturation processes. Cytochrome P450 pathway oxylipins from arachidonic acid, linoleic acid, alpha-linolenic acid and docosahexaenoic acid PUFAs are associated with AN diagnosis. The diol:epoxide ratios suggest the sEH activity is higher in AN compared with controls. Multivariate analysis illustrates normalization of lipidomic profiles in recovered ANs. EPHX2 influences AN risk through in vivo interaction with dietary PUFAs. PUFA composition and concentrations as well as sEH activity may contribute to the pathogenesis and prognosis of AN. Our data support the involvement of EPHX2-associated lipidomic and oxylipin dysregulations in AN, and reveal their potential as biomarkers to assess responsiveness to future intervention or treatment.
authors.affiliation: Department of Psychiatry, University of California at San Diego, San Diego, CA, USA.
authors.forename: P B
authors.initials: PB
authors.lastname: Shih
authors.affiliation: Department of Entomology, University of California at Davis, Davis, CA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Entomology, University of California at Davis, Davis, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Morisseau
authors.affiliation: Department of Entomology, University of California at Davis, Davis, CA, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: German
authors.affiliation: Cypher Genomics, San Diego, CA, USA.
authors.forename: A A Scott-Van
authors.initials: AA
authors.lastname: Zeeland
authors.affiliation: Department of Psychiatry, University of California at San Diego, San Diego, CA, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Armando
authors.affiliation: Department of Psychiatry, University of California at San Diego, San Diego, CA, USA.
authors.forename: O
authors.initials: O
authors.lastname: Quehenberger
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, CA, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Bergen
authors.affiliation: Division of Biological and Environmental Sciences and Engineering, KAUST, Thuwal, KSA and Brain Mind Institute, EPFL, Lausanne, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Magistretti
authors.affiliation: Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Berrettini
authors.affiliation: Department of Psychiatry, Cornell University, New York, NY, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Halmi
authors.affiliation: Department of Human Biology, J. Craig Venter Institute, San Diego, CA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Schork
authors.affiliation: Department of Entomology, University of California at Davis, Davis, CA, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Hammock
authors.affiliation: Department of Psychiatry, University of California at San Diego, San Diego, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Kaye
mesh_terms: D000293:Adolescent; D000328:Adult; D000856:Anorexia Nervosa / Q000097:blood / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004032:Diet; D004851:Epoxide Hydrolases / Q000235:genetics / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000097:blood / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D050356:Lipid Metabolism; D054883:Oxylipins / Q000097:blood / Q000378:metabolism
chemical_list: D005231:Fatty Acids, Unsaturated; D054883:Oxylipins; D004851:Epoxide Hydrolases; C506428:EPHX2 protein, human
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