Dysregulation of Amino Acid, Lipid, and Acylpyruvate Metabolism in Idiopathic Intracranial Hypertension: A Non-targeted Case Control and Longitudinal Metabolomic Study.
Dysregulation of Amino Acid, Lipid, and Acylpyruvate Metabolism in Idiopathic Intracranial Hypertension: A Non-targeted Case Control and Longitudinal Metabolomic Study.
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DOI：
10.1021/acs.jproteome.2c00449
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发表时间：
2023-04-07
影响因子：
4.4
通讯作者：
Sinclair, Alexandra J.
中科院分区：
文献类型：
--
作者：
Alimajstorovic, Zerin;Mollan, Susan P.;Grech, Olivia;Mitchell, James L.;Yiangou, Andreas;Thaller, Mark;Lyons, Hannah;Sassani, Matilde;Seneviratne, Senali;Hancox, Thomas;Jankevics, Andris;Najdekr, Lukas;Dunn, Warwick;Sinclair, Alexandra J.
关键词：
背景：特发性颅内高压(IIH)的特征是颅内压升高，主要发生在肥胖女性。其发病机制尚不清楚。我们应用超高效液相色谱-质谱仪的非靶向代谢分析，与对照组比较，对IIH患者的脑脊液(CSF)和血清进行了表征。方法和结果：样本来自IIH患者(n=66)，他们在治疗前和治疗后12个月时均有活动性疾病。对照样本来自性别和体重匹配的健康对照组(n=20)。我们确定了脑脊液中有注释的代谢物甲酰丙酮酸和顺丁烯二酸丙酮酸/延胡索丙酮酸，这些代谢物在IIH中的浓度比对照组低，并在体重减轻后恢复到对照组中观察到的值。这些代谢物在基线时的血清中显示出相反的趋势。单纯IIH患者血清和脑脊液中多种氨基酸代谢途径和脂类受到干扰。IIH患者血脂代谢途径明显增加。结论：与对照组相比，IIH患者观察到了许多与氨基酸、脂肪和酰丙酮酸代谢相关的不同代谢途径。这些途径与临床措施相关，并随着疾病缓解而正常化。这些代谢途径的扰动提供了对IIH疾病失调的初步了解。
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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影响因子：
5
作者：
Kabbouche, MA;Powers, SW;Hershey, AD
通讯作者：
Hershey, AD
影响因子：
2.7
作者：
Burow P;Meyer A;Naegel S;Watzke S;Zierz S;Kraya T
通讯作者：
Kraya T
影响因子：
4.5
作者：
Mohan S;Patel H;Bolinaga J;Soekamto N
通讯作者：
Soekamto N
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
4.9
作者：
Erdelyi-Botor, Szilvia;Komaromy, Hedvig;Pfund, Zoltan
通讯作者：
Pfund, Zoltan