Projects per year
Abstract
Background: Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure occurring predominantly in women with obesity. The pathogenesis is not understood. We have applied untargeted metabolomic analysis using ultrahigh-performance liquid chromatography–mass spectrometry to characterize the cerebrospinal fluid (CSF) and serum in IIH compared to control subjects. Methods and findings: Samples were collected from IIH patients (n = 66) with active disease at baseline and again at 12 months following therapeutic weight loss. Control samples were collected from gender- and weight-matched healthy controls (n = 20). We identified annotated metabolites in CSF, formylpyruvate and maleylpyruvate/fumarylpyruvate, which were present at lower concentrations in IIH compared to control subjects and returned to values observed in controls following weight loss. These metabolites showed the opposite trend in serum at baseline. Multiple amino acid metabolic pathways and lipid classes were perturbed in serum and CSF in IIH alone. Serum lipid metabolite pathways were significantly increased in IIH. Conclusions: We observed a number of differential metabolic pathways related to amino acid, lipid, and acylpyruvate metabolism, in IIH compared to controls. These pathways were associated with clinical measures and normalized with disease remission. Perturbation of these metabolic pathways provides initial understanding of disease dysregulation in IIH.
Original language | English |
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Number of pages | 11 |
Journal | Journal of Proteome Research |
Early online date | 19 Dec 2022 |
DOIs | |
Publication status | E-pub ahead of print - 19 Dec 2022 |
Keywords
- lipid metabolism
- arginine metabolism
- metabolomics
- intracranial pressure
- idiopathic intracranial hypertension
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Dive into the research topics of 'Dysregulation of amino acid, lipid and acylpyruvate metabolism in idiopathic intracranial hypertension: a non-targeted case control and longitudinal metabolomic study'. Together they form a unique fingerprint.Projects
- 3 Finished
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Integrating innovative technologies for genotyping in stratified medicine
Moss, P., Dunn, W., Beggs, A., Viant, M., Drayson, M., Adams, D., Bonifer, C. & Guenther, U.
1/04/15 → 1/07/18
Project: Research Councils
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Assessing the Therapeutic Efficacy of an 11Beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitor (AZD4017) in Idiopathic Intracranial Hypertension (IIH)
Sinclair, A., Tomlinson, J. & Stewart, P.
12/08/13 → 11/08/17
Project: Research Councils