PMID- 25824304
OWN - NLM
STAT- MEDLINE
DCOM- 20170117
LR  - 20240325
IS  - 1476-5578 (Electronic)
IS  - 1359-4184 (Print)
IS  - 1359-4184 (Linking)
VI  - 21
IP  - 4
DP  - 2016 Apr
TI  - Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia 
      nervosa.
PG  - 537-46
LID - 10.1038/mp.2015.26 [doi]
AB  - 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.
FAU - Shih, P B
AU  - Shih PB
AD  - Department of Psychiatry, University of California at San Diego, San Diego, CA, 
      USA.
FAU - Yang, J
AU  - Yang J
AD  - Department of Entomology, University of California at Davis, Davis, CA, USA.
FAU - Morisseau, C
AU  - Morisseau C
AD  - Department of Entomology, University of California at Davis, Davis, CA, USA.
FAU - German, J B
AU  - German JB
AD  - Department of Entomology, University of California at Davis, Davis, CA, USA.
FAU - Zeeland, A A Scott-Van
AU  - Zeeland AA
AD  - Cypher Genomics, San Diego, CA, USA.
FAU - Armando, A M
AU  - Armando AM
AD  - Department of Psychiatry, University of California at San Diego, San Diego, CA, 
      USA.
FAU - Quehenberger, O
AU  - Quehenberger O
AD  - Department of Psychiatry, University of California at San Diego, San Diego, CA, 
      USA.
FAU - Bergen, A W
AU  - Bergen AW
AD  - Center for Health Sciences, SRI International, Menlo Park, CA, USA.
FAU - Magistretti, P
AU  - Magistretti P
AD  - Division of Biological and Environmental Sciences and Engineering, KAUST, Thuwal, 
      KSA and Brain Mind Institute, EPFL, Lausanne, Switzerland.
FAU - Berrettini, W
AU  - Berrettini W
AD  - Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Halmi, K A
AU  - Halmi KA
AD  - Department of Psychiatry, Cornell University, New York, NY, USA.
FAU - Schork, N
AU  - Schork N
AD  - Department of Human Biology, J. Craig Venter Institute, San Diego, CA, USA.
FAU - Hammock, B D
AU  - Hammock BD
AD  - Department of Entomology, University of California at Davis, Davis, CA, USA.
FAU - Kaye, W
AU  - Kaye W
AD  - Department of Psychiatry, University of California at San Diego, San Diego, CA, 
      USA.
LA  - eng
GR  - U24DK097154/DK/NIDDK NIH HHS/United States
GR  - 1K01DK087813-01A1/DK/NIDDK NIH HHS/United States
GR  - R01 MH106781/MH/NIMH NIH HHS/United States
GR  - R01 ES002710/ES/NIEHS NIH HHS/United States
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - U24 DK097154/DK/NIDDK NIH HHS/United States
GR  - K01 DK087813/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150331
PL  - England
TA  - Mol Psychiatry
JT  - Molecular psychiatry
JID - 9607835
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Oxylipins)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - EC 3.3.2.10 (EPHX2 protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Anorexia Nervosa/blood/enzymology/genetics/*metabolism
MH  - Case-Control Studies
MH  - Cross-Sectional Studies
MH  - Diet
MH  - Epoxide Hydrolases/genetics/*metabolism
MH  - Fatty Acids, Unsaturated/blood/metabolism
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Humans
MH  - Lipid Metabolism
MH  - Oxylipins/blood/metabolism
PMC - PMC4591075
MID - NIHMS658414
COIS- Disclosures of Conflict of Interest: None of the authors has any conflict of 
      interest to report.
EDAT- 2015/04/01 06:00
MHDA- 2017/01/18 06:00
PMCR- 2016/05/18
CRDT- 2015/04/01 06:00
PHST- 2014/09/16 00:00 [received]
PHST- 2015/01/13 00:00 [revised]
PHST- 2015/01/23 00:00 [accepted]
PHST- 2015/04/01 06:00 [entrez]
PHST- 2015/04/01 06:00 [pubmed]
PHST- 2017/01/18 06:00 [medline]
PHST- 2016/05/18 00:00 [pmc-release]
AID - mp201526 [pii]
AID - 10.1038/mp.2015.26 [doi]
PST - ppublish
SO  - Mol Psychiatry. 2016 Apr;21(4):537-46. doi: 10.1038/mp.2015.26. Epub 2015 Mar 31.