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Metabolomics profiles of patients with Wilson disease reveal a distinct metabolic signature.

ABSTRACT: INTRODUCTION:Wilson disease (WD) is characterized by excessive intracellular copper accumulation in liver and brain due to defective copper biliary excretion. With highly varied phenotypes and a lack of biomarkers for the different clinical manifestations, diagnosis and treatment can be difficult. OBJECTIVE:The aim of the present study was to analyze serum metabolomics profiles of patients with Wilson disease compared to healthy subjects, with the goal of identifying differentially abundant metabolites as potential biomarkers for this condition. METHODS:Hydrophilic interaction liquid chromatography-quadrupole time of flight mass spectrometry was used to evaluate the untargeted serum metabolome of 61 patients with WD (26 hepatic and 25 neurologic subtypes, 10 preclinical) compared to 15 healthy subjects. We conducted analysis of covariance with potential confounders (body mass index, age, sex) as covariates and partial least-squares analysis. RESULTS:After adjusting for clinical covariates and multiple testing, we identified 99 significantly different metabolites (FDR?

SUBMITTER: Sarode GV

PROVIDER: S-EPMC6568258 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Metabolomics profiles of patients with Wilson disease reveal a distinct metabolic signature.

Sarode Gaurav V GV Kim Kyoungmi K Kieffer Dorothy A DA Shibata Noreene M NM Litwin Tomas T Czlonkowska Anna A Medici Valentina V

Metabolomics : Official journal of the Metabolomic Society 20190312 3

<h4>Introduction</h4>Wilson disease (WD) is characterized by excessive intracellular copper accumulation in liver and brain due to defective copper biliary excretion. With highly varied phenotypes and a lack of biomarkers for the different clinical manifestations, diagnosis and treatment can be difficult.<h4>Objective</h4>The aim of the present study was to analyze serum metabolomics profiles of patients with Wilson disease compared to healthy subjects, with the goal of identifying differentiall ...[more]

PMID: 30868361

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Project description:Acute social defeat represents a naturalistic form of conditioned fear and is an excellent model in which to investigate the biological basis of stress resilience. While there is growing interest in identifying biomarkers of stress resilience, until recently, it has not been feasible to associate levels of large numbers of neurochemicals and metabolites to stress-related phenotypes. The objective of the present study was to use an untargeted metabolomics approach to identify known and unknown neurochemicals in select brain regions that distinguish susceptible and resistant individuals in two rodent models of acute social defeat. In the first experiment, male mice were first phenotyped as resistant or susceptible. Then, mice were subjected to acute social defeat, and tissues were immediately collected from the ventromedial prefrontal cortex (vmPFC), basolateral/central amygdala (BLA/CeA), nucleus accumbens (NAc), and dorsal hippocampus (dHPC). Ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS) was used for the detection of water-soluble neurochemicals. In the second experiment, male Syrian hamsters were paired in daily agonistic encounters for 2 weeks, during which they formed stable dominant-subordinate relationships. Then, 24 h after the last dominance encounter, animals were exposed to acute social defeat stress. Immediately after social defeat, tissue was collected from the vmPFC, BLA/CeA, NAc, and dHPC for analysis using UPLC-HRMS. Although no single biomarker characterized stress-related phenotypes in both species, commonalities were found. For instance, in both model systems, animals resistant to social defeat stress also show increased concentration of molecules to protect against oxidative stress in the NAc and vmPFC. Additionally, in both mice and hamsters, unidentified spectral features were preliminarily annotated as potential targets for future experiments. Overall, these findings suggest that a metabolomics approach can identify functional groups of neurochemicals that may serve as novel targets for the diagnosis, treatment, or prevention of stress-related mental illness.

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Metabolomics profiles of patients with Wilson disease reveal a distinct metabolic signature.

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Metabolomics profiles of patients with Wilson disease reveal a distinct metabolic signature.

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