System-wide assembly of pathways and modules hierarchically reveal metabolic mechanism of cerebral ischemia

Zhu, Yan; Guo, Zhiyong; Zhang, Liangxiao; Zhang, Yingying; Chen, Yinying; Nan, Jingyi; Zhao, Buchang; Xiao, Hongbin; Wang, Zhong; Wang, Yongyan

doi:10.1038/srep17068

Cited by 19 publications

(14 citation statements)

References 62 publications

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“…Amino acids were also affected, with obese animals showing reductions in tyrosine and methionine, and an increase in taurine. Similar changes in plasma amino acids have been reported as biomarkers for ischaemic stroke in both patients and rodents, although the directions of these changes vary ( Gao et al, 2013 ; Kimberly et al, 2013 ; Liu et al, 2015 ; Zhu et al, 2015 ). Because the extent of these changes can correlate with the severity of ischaemic damage ( Kimberly et al, 2013 ), the difference between obese and control animals found here could be due to increased ischaemic damage in obese mice.…”

Section: Discussionsupporting

confidence: 65%

“…Further changes in glycerophospholipids and lysophospholipids were found in addition to those altered by obese mice in the absence of stroke. LysoPC(20:4) was increased in obese mice relative to control mice after stroke, and is a reported biomarker of ischaemic stroke in patients ( Jové et al, 2015 ; Zhu et al, 2015 ). Stroke also affected long-chain sphingomyelin (SM) sphingolipids in obese animals.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies in animal models and humans have applied metabolomic approaches to understand the molecular pathophysiology of stroke and have highlighted specific important areas of metabolism. These include specific changes in amino acids, fatty acids, sphingolipids, and lysophospholipid species ( Gao et al, 2013 ; Jové et al, 2015 ; Kimberly et al, 2013 ; Liu et al, 2015 ; Sheth et al, 2015 ; Zhu et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Adipose tissue, metabolic and inflammatory responses to stroke are altered in obese mice

Haley

Mullard

Hollywood

et al. 2017

Disease Models &Amp; Mechanisms

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Obesity is an independent risk factor for stroke, although several clinical studies have reported that obesity improves stroke outcome. Obesity is hypothesised to aid recovery by protecting against post-stroke catabolism. We therefore assessed whether obese mice had an altered metabolic and inflammatory response to stroke. Obese ob/ob mice underwent a 20-min middle cerebral artery occlusion and 24-h reperfusion. Lipid metabolism and expression of inflammatory cytokines were assessed in the plasma, liver and adipose tissue. The obese-specific metabolic response to stroke was assessed in plasma using non-targeted ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) metabolomics coupled with univariate and multivariate analysis. Obesity had no effect on the extent of weight loss 24 h after stroke but affected the metabolic and inflammatory responses to stroke, predominantly affecting lipid metabolism. Specifically, obese mice had increases in plasma free fatty acids and expression of adipose lipolytic enzymes. Metabolomics identified several classes of metabolites affected by stroke in obese mice, including fatty acids and membrane lipids (glycerophospholipids, lysophospholipids and sphingolipids). Obesity also featured increases in inflammatory cytokines in the plasma and adipose tissue. Overall, these results demonstrate that obesity affected the acute metabolic and inflammatory response to stroke and suggest a potential role for adipose tissue in this effect. These findings could have implications for longer-term recovery and also further highlight the importance of considering comorbidities in preclinical stroke research, especially when identifying biomarkers for stroke. However, further work is required to assess whether these changes translate into long-term effects on recovery.

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Section: Discussionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adipose tissue, metabolic and inflammatory responses to stroke are altered in obese mice

Haley

Mullard

Hollywood

et al. 2017

Disease Models &Amp; Mechanisms

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“…To identify the most relevant pathways, the threshold of impact value from the pathway analysis via MetaboAnalyst 3.0 is set at 0.10 [ 24 ]. Seven pathways (Figure 7A , Table 5 ) among the regulated pathways are filtered out as potential target pathways for TBI on day 1, four pathways (Figure 7C , Table 5 ) for TBI on day 3, two pathways for XFZY on day 1 (Figure 7B , Table 5 ), and three pathways for XFZY on day 3 (Figure 7D , Table 5 ).…”

Section: Resultsmentioning

confidence: 99%

Metabolomics reveals the effect of Xuefu Zhuyu Decoction on plasma metabolism in rats with acute traumatic brain injury

et al. 2017

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Xuefu Zhuyu Decoction (XFZY), an important traditional Chinese herbal formula, has been reported effective on traumatic brain injury (TBI) in rats. However, its cerebral protection mechanism has not been clarified at the metabolic level. This work aims to explore the global metabolic characteristics of XFZY in rats during the acute phase of TBI on days 1 and 3. A plasma metabolomics method based on gas chromatography-mass spectrometry coupled with univariate analysis and multivariate statistical analysis was performed in three groups (Sham, Vehicle, XFZY). Then, a pathway analysis using MetaboAnalyst 3.0 was performed to illustrate the pathways of therapeutic action of XFZY in TBI. XFZY treatment attenuates neurological dysfunction and cortical lesion volume post-injury on day 3, and reverses the plasma metabolite abnormalities (glutamic acid, lactic acid, 3-hydroxybutyric acid, and ribitol, etc.). These differential metabolites are mainly involved in D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and inositol phosphate metabolism. Our study reveals potential biomarkers and metabolic networks of acute TBI and neuroprotection effects of XFZY, and shows this metabolomics approach with MetaboAnalyst would be a feasible way to systematically study therapeutic effects of XFZY on TBI.

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“…html;Karnovsky et al 2012). Markov clustering based module analysis was performed to analyze the complex biological network(Zhu et al 2015).…”

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confidence: 99%

Identification of serum metabolic markers for diagnosis of women with dormant genital tuberculosis

et al. 2016

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Introduction Genital tuberculosis (GTB) in women is one of the common causes of infertility in emerging countries. As an intracellular pathogen, Mycobacterium tuberculosis in the endometrium significantly alters the host metabolism in dormant GTB cases. Nuclear magnetic resonance (NMR) based metabolic profiling has emerged as a useful tool for identification of biomarkers in biological fluids. Objective To investigate NMR based serum metabolic profile of dormant GTB women as compared to controls. Methods Dormant GTB women (n = 26) and unexplained infertile women (controls; n = 26), healthy proven fertile women undergoing voluntary sterilization (n = 25) and women undergoing recurrent spontaneous miscarriage (RSM) (n = 27) were included in the study. 700 MHz proton NMR spectra of serum collected from these patients were recorded. Multivariate analysis including principal component analysis, partial least squares discriminant analysis and orthogonal projection to latent structurediscriminant analysis was applied to all the spectra. Association of dysregulated serum metabolites with our earlier findings related to altered endometrial tissue metabolites in dormant GTB women was studied using multiple correlation analysis. Results This study indicates a clear metabolic differentiation between women with dormant GTB and controls. Metabolites including 3-hydroxybutyrate, succinate, citrate, acetate, L-glutamine, L-lysine, glutamate, L-threonine and 1-methyl histidine were found to be significantly upregulated in serum of women with dormant GTB compared with controls. Pearson's correlation analysis showed a significant correlation between the expression of endometrial tissue and serum metabolites. Conclusions The set of identified metabolites may be considered as candidate markers for the diagnosis of dormant GTB and help clinicians in early therapeutic management.

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System-wide assembly of pathways and modules hierarchically reveal metabolic mechanism of cerebral ischemia

Cited by 19 publications

References 62 publications

Adipose tissue, metabolic and inflammatory responses to stroke are altered in obese mice

Adipose tissue, metabolic and inflammatory responses to stroke are altered in obese mice

Metabolomics reveals the effect of Xuefu Zhuyu Decoction on plasma metabolism in rats with acute traumatic brain injury

Identification of serum metabolic markers for diagnosis of women with dormant genital tuberculosis

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