Dysregulation of amino acid, lipid, and acylpyruvate metabolism in idiopathic intracranial hypertension : a non-targeted case control and longitudinal metabolomic study.
Alimajstorovic, Zerin Mollan, Susan P Grech, Olivia Mitchell, James L Yiangou, Andreas Thaller, Mark Lyons, Hannah Sassani, Matilde Seneviratne, Senali Hancox, Thomas
Alimajstorovic, Zerin
Mollan, Susan P
Grech, Olivia
Mitchell, James L
Yiangou, Andreas
Thaller, Mark
Lyons, Hannah
Sassani, Matilde
Seneviratne, Senali
Hancox, Thomas
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2022-12-19
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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.
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Alimajstorovic Z, Mollan SP, Grech O, Mitchell JL, Yiangou A, Thaller M, Lyons H, Sassani M, Seneviratne S, Hancox T, Jankevics A, Najdekr L, Dunn W, Sinclair AJ. Dysregulation of Amino Acid, Lipid, and Acylpyruvate Metabolism in Idiopathic Intracranial Hypertension: A Non-targeted Case Control and Longitudinal Metabolomic Study. J Proteome Res. 2023 Apr 7;22(4):1127-1137. doi: 10.1021/acs.jproteome.2c00449. Epub 2022 Dec 19.
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