Balancing metabolome coverage and reproducibility for untargeted NMR-based metabolic profiling in tissue samples through mixture design methods

Zheng, Hong; Ni, Zhitao; Cai, Aimin; Zhang, Xi; Chen, Jiuxia; Shu, Qi; Gao, Hongchang

doi:10.1007/s00216-018-1396-9

Cited by 13 publications

(8 citation statements)

References 31 publications

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“…Table S1 presents the overall list of assigned peaks (52 in total) and corresponding information regarding metabolite predominance in each type of tissue. In general, our results are consistent with previous reports of 1 H NMR spectra of kidney [44,45,46] and liver extracts [46,47,48,49], adding new information regarding the polar metabolome of mice kidney (namely, changes in the levels of inosine monophosphate (IMP), uridine monophosphate (UMP), allantoin, threonine, 3-hydroxyisobutyrate (3-HIBA), trimethylamine N -oxide (TMAO), uridine diphosphate-glucuronate (UDP-GlcA)), liver (asparagine, glycerophosphocholine (GPC), hypoxanthine, hippurate, IMP, threonine, 3-HIBA, TMAO, and UDP-GlcA), and breast tissue, for which, to our knowledge, no previous 1 H NMR metabolomics study has been reported. By visual inspection of the spectra in Figure 1, it becomes clear that alanine, lactate, and taurine predominate in all three tissue types, whereas specific characteristics are noted, as expected, for different tissues: (1) kidney comprises relatively high levels of betaine, m -inositol, and inosine, (2) liver shows high levels of acetone, glucose, glycogen, and glutathione (reduced form, GSH), and (3) breast tissue shows high levels of creatine, phosphocholine, and glycerol moieties arising from glycerolipids.…”

Section: Resultssupporting

confidence: 94%

Multi-Organ NMR Metabolomics to Assess In Vivo Overall Metabolic Impact of Cisplatin in Mice

et al. 2019

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This work describes, to our knowledge, the first NMR metabolomics analysis of mice kidney, liver, and breast tissue in response to cisplatin exposure, in search of early metabolic signatures of cisplatin biotoxicity. Balb/c mice were exposed to a single 3.5 mg/kg dose of cisplatin and then euthanized; organs (kidney, liver, breast tissue) were collected at 1, 12, and 48 h. Polar tissue extracts were analyzed by NMR spectroscopy, and the resulting spectra were studied by multivariate and univariate analyses. The results enabled the identification of the most significant deviant metabolite levels at each time point, and for each tissue type, and showed that the largest metabolic impact occurs for kidney, as early as 1 h post-injection. Kidney tissue showed a marked depletion in several amino acids, comprised in an overall 13-metabolites signature. The highest number of changes in all tissues was noted at 12 h, although many of those recovered to control levels at 48 h, with the exception of some persistently deviant tissue-specific metabolites, thus enabling the identification of relatively longer-term effects of cDDP. This work reports, for the first time, early (1–48 h) concomitant effects of cDDP in kidney, liver, and breast tissue metabolism, thus contributing to the understanding of multi-organ cDDP biotoxicity.

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Section: Resultssupporting

confidence: 94%

Multi-Organ NMR Metabolomics to Assess In Vivo Overall Metabolic Impact of Cisplatin in Mice

et al. 2019

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“…Typical 1 H-NMR CPMG (600 MHz) spectra of different brain regions (midbrain, cortex, striatum, hippocampus, cerebellum, and hypothalamus, respectively), obtained from control, PD and LID rats are presented in Figure 2. Assignments were performed according to our previous studies (Zheng et al, 2017(Zheng et al, , 2018a using the Chenomx NMR suite 7.0 (Chenomx Inc., Edmonton, AB, Canada). A total of 20 metabolites were identified, which can be detected in all six brain regions (Figure 2).…”

Section: Nmr-based Metabolic Profiling Of Different Brain Regionsmentioning

confidence: 99%

Brain-Region Specific Metabolic Abnormalities in Parkinson’s Disease and Levodopa-Induced Dyskinesia

Yang

Zhang

Wang

et al. 2020

Front. Aging Neurosci.

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Several lines of evidence point to alteration in brain metabolic homeostasis in Parkinson's disease (PD) and levodopa-induced dyskinesia (LID), yet the metabolic mechanism in different brain regions underlying PD and LID remains largely unknown. The present study aimed to uncover the metabolic pathways across anatomical regions in the brain of PD and LID. Using an NMR-based metabolomic approach, we generated the metabolomics profiling data from six different brain regions of PD rats and following the onset of LIDs. The diversity of metabolite patterns across the brain and its relation to PD and LID were further investigated through principal component analysis (PCA) and multivariate general linear model. Compared with control rats, dopamine loss in PD rats produced a marked and persistent metabolic disturbance in neurotransmitter metabolism and energy pathway, resulting in a metabolic imbalance among different brain regions. In LID rats, levodopa replacement did not restore the midbrain-striatum metabolic crosstalk and metabolic disturbance throughout the brain was involved in levodopa related involuntary movements. Most notably, the midbrain and right cortex were identified as the primary regions of metabolic abnormalities in PD and LID rats. Neurochemical differences in metabolic phenotypes were mainly defined by various neurotransmitters including glutamate, glutamine and aspartate. Accordingly, we found that the PD and LID rats exhibited lower levels of synaptophysin (SYP), a marker for synaptic plasticity, compared with control rats. These findings provide key insights into the metabolic mechanism underlying PD and LID by defining brain-region specific metabolic phenotype, with implications for developing targeted therapies.

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“…Metabolite extraction from tissue samples was conducted using the reported method in our previous study. 23 Briefly, the frozen tissue was weighted into an centrifuge tube, and then, 4 mL/g of methanol and 0.85 mL/g of distilled water was added according to tissue weight and homogenized using a handheld homogenizer (Fluko F8, Essen, German). Subsequently, 2 mL/g of chloroform and 2 mL/g of distilled water were added and vortexed for 30 s. The mixture was kept on ice for 15 min and centrifuged at 10,000g for 15 min at 4 °C.…”

Section: Tissue Sample Collection and Preparationmentioning

confidence: 99%

“…Subsequently, we aligned all NMR spectra obtained from the same tissue sample by using the "icoshif t" procedure under MATLAB environment (R2012a, The Mathworks Inc., MA, USA). 24 NMR signals were assigned on the basis of the reported data 23 and the Human Metabolome Database. 25 To further confirm tentative identifications, a 13 C− 1 H heteronuclear single quantum coherence experiment was employed for the typical samples.…”

Section: H-nmr-based Metabolomics Analysismentioning

confidence: 99%

Sex-Specific Metabolic Changes in Peripheral Organs of Diabetic Mice

Zhang

Ning

et al. 2020

J. Proteome Res.

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Diabetes mellitus (DM) can cause systemic metabolic disorders, but the impact of gender on DM-related metabolic changes is rarely reported. Herein, we analyzed metabolic alterations in the heart, liver, and kidney of male and female mice from normal to diabetes via a 1H NMR-based metabolomics method and aimed to investigate sex-specific metabolic mechanisms underlying the onset and development of diabetes and its complications. Our results demonstrate that male mice had more significant metabolic disorders from normal to diabetes than female mice. Moreover, the kidney was found as the major organ of metabolic disorders during the development of diabetes, followed by the liver and heart. These altered metabolites were mainly implicated in energy metabolism as well as amino acid, choline, and nucleotide metabolism. Therefore, this study suggests that the kidney is the primary organ affected by diabetes in a sex-specific manner, which provides a metabolic view on the pathogenesis of diabetic kidney diseases between genders.

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Balancing metabolome coverage and reproducibility for untargeted NMR-based metabolic profiling in tissue samples through mixture design methods

Cited by 13 publications

References 31 publications

Multi-Organ NMR Metabolomics to Assess In Vivo Overall Metabolic Impact of Cisplatin in Mice

Multi-Organ NMR Metabolomics to Assess In Vivo Overall Metabolic Impact of Cisplatin in Mice

Brain-Region Specific Metabolic Abnormalities in Parkinson’s Disease and Levodopa-Induced Dyskinesia

Sex-Specific Metabolic Changes in Peripheral Organs of Diabetic Mice

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