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    Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa

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    Type
    Article
    Authors
    Shih, P. B.
    Yang, J.
    Morisseau, C.
    German, J. B.
    Scott-Van Zeeland, A. A.
    Armando, A. M.
    Quehenberger, O.
    Bergen, A. W.
    Magistretti, Pierre J. cc
    Berrettini, W.
    Halmi, K. A.
    Schork, N.
    Hammock, B. D.
    Kaye, W.
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Date
    2015-03-31
    Online Publication Date
    2015-03-31
    Print Publication Date
    2016-04
    Embargo End Date
    2015-10-01
    Permanent link to this record
    http://hdl.handle.net/10754/622393
    
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    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.
    Citation
    Shih PB, Yang J, Morisseau C, German JB, Zeeland AAS-V, et al. (2015) Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa. Molecular Psychiatry 21: 537–546. Available: http://dx.doi.org/10.1038/mp.2015.26.
    Sponsors
    This work was supported, in part, by National Institutes of Health (NIH/NIDDK) Career Development Award Grant (1K01DK087813-01A1-Shih); NIH West Coast Metabolomics Center Pilot Grant (Shih); Price Foundation of Geneva, Switzerland; NIH U24 DK097154/DK/NIDDK; NIEHS R01 ES002710 and NIEHS/Superfund Research Program P42 ES004699. We acknowledge the special help with PUFA data management provided by Yan Wang, and the Price Foundation study collaborators for providing the clinical data and biospecimens for this study.
    Publisher
    Springer Nature
    Journal
    Molecular Psychiatry
    DOI
    10.1038/mp.2015.26
    Additional Links
    http://europepmc.org/articles/pmc4591075?pdf=render
    ae974a485f413a2113503eed53cd6c53
    10.1038/mp.2015.26
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program

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