Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa

P. B. Shih, J. Yang, C. Morisseau, J. B. German, A. A Scott Van Zeeland, A. M. Armando, O. Quehenberger, A. W. Bergen, P. Magistretti, W. Berrettini, K. A. Halmi, N. Schork, B. D. Hammock, W. Kaye

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.Molecular Psychiatry advance online publication, 31 March 2015; doi:10.1038/mp.2015.26.

Original languageEnglish (US)
JournalMolecular Psychiatry
DOIs
StateAccepted/In press - Mar 31 2015

Fingerprint

Epoxide Hydrolases
Anorexia Nervosa
Oxylipins
Unsaturated Fatty Acids
Epoxy Compounds
Biomarkers
alpha-Linolenic Acid
Metabolomics
Docosahexaenoic Acids
Omega-3 Fatty Acids
Proxy
Arachidonic Acid
Cytochrome P-450 Enzyme System

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Shih, P. B., Yang, J., Morisseau, C., German, J. B., Zeeland, A. A. S. V., Armando, A. M., ... Kaye, W. (Accepted/In press). Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa. Molecular Psychiatry. https://doi.org/10.1038/mp.2015.26

Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa. / Shih, P. B.; Yang, J.; Morisseau, C.; German, J. B.; Zeeland, A. A Scott Van; Armando, A. M.; Quehenberger, O.; Bergen, A. W.; Magistretti, P.; Berrettini, W.; Halmi, K. A.; Schork, N.; Hammock, B. D.; Kaye, W.

In: Molecular Psychiatry, 31.03.2015.

Research output: Contribution to journalArticle

Shih, PB, Yang, J, Morisseau, C, German, JB, Zeeland, AASV, Armando, AM, Quehenberger, O, Bergen, AW, Magistretti, P, Berrettini, W, Halmi, KA, Schork, N, Hammock, BD & Kaye, W 2015, 'Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa', Molecular Psychiatry. https://doi.org/10.1038/mp.2015.26
Shih, P. B. ; Yang, J. ; Morisseau, C. ; German, J. B. ; Zeeland, A. A Scott Van ; Armando, A. M. ; Quehenberger, O. ; Bergen, A. W. ; Magistretti, P. ; Berrettini, W. ; Halmi, K. A. ; Schork, N. ; Hammock, B. D. ; Kaye, W. / Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa. In: Molecular Psychiatry. 2015.
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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.Molecular Psychiatry advance online publication, 31 March 2015; doi:10.1038/mp.2015.26.",
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