Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa.
- Shih PB Department of Psychiatry, University of California at San Diego, San Diego, CA, USA.
- Yang J Department of Entomology, University of California at Davis, Davis, CA, USA.
- Morisseau C Department of Entomology, University of California at Davis, Davis, CA, USA.
- German JB Department of Entomology, University of California at Davis, Davis, CA, USA.
- Zeeland AA Cypher Genomics, San Diego, CA, USA.
- Armando AM Department of Psychiatry, University of California at San Diego, San Diego, CA, USA.
- Quehenberger O Department of Psychiatry, University of California at San Diego, San Diego, CA, USA.
- Bergen AW Center for Health Sciences, SRI International, Menlo Park, CA, USA.
- Magistretti P Division of Biological and Environmental Sciences and Engineering, KAUST, Thuwal, KSA and Brain Mind Institute, EPFL, Lausanne, Switzerland.
- Berrettini W Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
- Halmi KA Department of Psychiatry, Cornell University, New York, NY, USA.
- Schork N Department of Human Biology, J. Craig Venter Institute, San Diego, CA, USA.
- Hammock BD Department of Entomology, University of California at Davis, Davis, CA, USA.
- Kaye W Department of Psychiatry, University of California at San Diego, San Diego, CA, USA.
- 2015-04-01
Published in:
- Molecular psychiatry. - 2016
Adolescent
Adult
Anorexia Nervosa
Case-Control Studies
Cross-Sectional Studies
Diet
Epoxide Hydrolases
Fatty Acids, Unsaturated
Female
Genetic Predisposition to Disease
Humans
Lipid Metabolism
Oxylipins
English
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.
- Language
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- English
- Open access status
- green
- Identifiers
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- DOI 10.1038/mp.2015.26
- PMID 25824304
- Persistent URL
- https://sonar.ch/global/documents/186293
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