학술논문

Dysregulation of soluble epoxide hydrolase and lipidomic profiles in anorexia nervosa
Document Type
article
Source
Molecular Psychiatry. 21(4)
Subject
Biomedical and Clinical Sciences
Clinical Sciences
Behavioral and Social Science
Prevention
Eating Disorders
Serious Mental Illness
Mental Illness
Anorexia
Clinical Research
Brain Disorders
Nutrition
Mental Health
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
Biological Sciences
Medical and Health Sciences
Psychology and Cognitive Sciences
Psychiatry
Clinical sciences
Biological psychology
Clinical and health psychology
Language
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.