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Depressive symptoms in non-alcoholic fatty liver disease are identified by perturbed lipid and lipoprotein metabolism

Abstract:
Non-alcoholic fatty liver disease (NAFLD) and depression are common disorders and have bidirectional contributing relationships to metabolic syndrome. We aimed to determine whether a fasting serum signature of recent, self-reported depressive symptoms could be identified in a heterogeneous NAFLD cohort using nuclear magnetic resonance (NMR)-based metabolomics integrated with clinical chemistry. Serum nuclear magnetic resonance (NMR) metabolite profiles and corresponding clinical chemistry were compared between patients with depressive symptoms in the last 12-months (n = 81) and patients without recent depressive symptoms (n = 137 controls) using multivariate statistics. Orthogonal partial least squares discriminant analysis (OPLS-DA) of the biochemical and metabolomic data identified NAFLD patients with recent depression with a cross-validated accuracy of 61.5%, independent of age, sex, medication, and other comorbidities. This led to the development of a diagnostic algorithm with AUC 0.83 for future testing in larger clinical cohorts. Serum triglycerides, VLDL cholesterol, and the inflammatory biomarker GlycA were key metabolites increased in patients with recent depressive symptoms, while serum glutamine level was reduced. Here, serum NMR metabolite analysis provides a link between disturbed lipid metabolism, inflammation, and active mental health issues in NAFLD, irrespective of disease severity.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1371/journal.pone.0261555

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Institution:
University of Oxford
Role:
Author
ORCID:
0000-0001-8781-7459
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Role:
Author
ORCID:
0000-0002-2433-6794
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Role:
Author
ORCID:
0000-0002-6716-1605
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Role:
Author
ORCID:
0000-0001-7886-8844
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Role:
Author
ORCID:
0000-0002-2072-9216


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Funder identifier:
10.13039/501100007723
Grant:
MSD1920_APP-ID_1238189
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Funder identifier:
10.13039/100010371
Grant:
MSD1920_APP-ID_1238189


Publisher:
Public Library of Science
Journal:
PLoS ONE More from this journal
Volume:
17
Issue:
1
Pages:
e0261555-e0261555
Publication date:
2022-01-06
DOI:
EISSN:
1932-6203
ISSN:
1932-6203


Language:
English
Keywords:
Pubs id:
1231475
Local pid:
pubs:1231475
Source identifiers:
W4205987226
Deposit date:
2026-04-09
ARK identifier:
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