Effects of Acute Systematic Hypoxia on Human Urinary Metabolites Using LC-MS-Based Metabolomics

Lou, Bih‐Show; Wu, Po Kuei; Liu, Yitong

doi:10.1089/ham.2013.1130

Cited by 22 publications

(25 citation statements)

References 49 publications

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“…It was previously reported that adenosine was released by hypoxic canine lung tissue and the levels of inosine and hypoxanthine showed sustained significant increases 31 , which is consistent with our results. In addition, an increased purine metabolism flux induced by acute systematic hypoxia has also been observed in a recently reported LC-MS study 32 . These data suggests that perturbed purine metabolism is implicated in HAPE.…”

Section: Discussionsupporting

confidence: 60%

Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

Guo

Tan

Liu³

et al. 2015

Sci Rep

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High-altitude pulmonary edema (HAPE) is a potentially fatal condition, occurring at altitudes greater than 3,000 m and affecting rapidly ascending, non-acclimatized healthy individuals. However, the lack of biomarkers for this disease still constitutes a bottleneck in the clinical diagnosis. Here, ultra-high performance liquid chromatography coupled with Q-TOF mass spectrometry was applied to study plasma metabolite profiling from 57 HAPE and 57 control subjects. 14 differential plasma metabolites responsible for the discrimination between the two groups from discovery set (35 HAPE subjects and 35 healthy controls) were identified. Furthermore, 3 of the 14 metabolites (C8-ceramide, sphingosine and glutamine) were selected as candidate diagnostic biomarkers for HAPE using metabolic pathway impact analysis. The feasibility of using the combination of these three biomarkers for HAPE was evaluated, where the area under the receiver operating characteristic curve (AUC) was 0.981 and 0.942 in the discovery set and the validation set (22 HAPE subjects and 22 healthy controls), respectively. Taken together, these results suggested that this composite plasma metabolite signature may be used in HAPE diagnosis, especially after further investigation and verification with larger samples.

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Section: Discussionsupporting

confidence: 60%

Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

Guo

Tan

Liu³

et al. 2015

Sci Rep

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“…() reported increased concentrations of blood lactate, succinate and citrate in 60 healthy male volunteers exposed to an altitude of 5300 m. It is likely that differences between our findings and those of Liao et al. () are methodological in nature, because varying effects on metabolic pathways have been observed between moderate (2000–3000 m) and high (3000–5500 m) altitudes (Lou et al., ). The use of moderate altitude exposure in the present study would probably have promoted different physiological responses when compared with studies completed at higher altitudes, albeit that athletes favour the use of moderate altitude so that they can continue to train effectively (Chapman, Stickford, & Levine, ).…”

Section: Discussioncontrasting

confidence: 58%

“…altitudes (Lou et al, 2014). The use of moderate altitude exposure in F I G U R E 4 Spring-embedded correlation plot illustrating metabolites (circles) and the associated correlations (lines/springs).…”

Section: Discussionmentioning

confidence: 99%

Characterizing the plasma metabolome during 14 days of live‐high, train‐low simulated altitude: A metabolomic approach

Lawler

Abbiss

Gummer

et al. 2018

Experimental Physiology

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New Findings What is the central question of this study?Does 14 days of live‐high, train‐low simulated altitude alter an individual's metabolomic/metabolic profile? What is the main finding and its importance?This study demonstrated that ∼200 h of moderate simulated altitude exposure resulted in greater variance in measured metabolites between subject than within subject, which indicates individual variability during the adaptive phase to altitude exposure. In addition, metabolomics results indicate that altitude alters multiple metabolic pathways, and the time course of these pathways is different over 14 days of altitude exposure. These findings support previous literature and provide new information on the acute adaptation response to altitude. Abstract The purpose of this study was to determine the influence of 14 days of normobaric hypoxic simulated altitude exposure at 3000 m on the human plasma metabolomic profile. For 14 days, 10 well‐trained endurance runners (six men and four women; 29 ± 7 years of age) lived at 3000 m simulated altitude, accumulating 196.4 ± 25.6 h of hypoxic exposure, and trained at ∼600 m. Resting plasma samples were collected at baseline and on days 3 and 14 of altitude exposure and stored at −80°C. Plasma samples were analysed using liquid chromatography–high‐resolution mass spectrometry to construct a metabolite profile of altitude exposure. Mass spectrometry of plasma identified 36 metabolites, of which eight were statistically significant (false discovery rate probability 0.1) from baseline to either day 3 or day 14. Specifically, changes in plasma metabolites relating to amino acid metabolism (tyrosine and proline), glycolysis (adenosine) and purine metabolism (adenosine) were observed during altitude exposure. Principal component canonical variate analysis showed significant discrimination between group means (P < 0.05), with canonical variate 1 describing a non‐linear recovery trajectory from baseline to day 3 and then back to baseline by day 14. Conversely, canonical variate 2 described a weaker non‐recovery trajectory and increase from baseline to day 3, with a further increase from day 3 to 14. The present study demonstrates that metabolomics can be a useful tool to monitor metabolic changes associated with altitude exposure. Furthermore, it is apparent that altitude exposure alters multiple metabolic pathways, and the time course of these changes is different over 14 days of altitude exposure.

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“…Emerging studies on animal model have highlighted the importance to recognize the metabolic fingerprint in perinatal anoxia-hypoxia (19)(20)(21). In newborns with perinatal asphyxia, a small number of metabolomics studies have been published in the literature (22)(23)(24)(25)(26)(27); each of them has depicted the metabolic snapshot of the disease. As recapitulated in a recent review (28), human metabolomics studies have found that the most impaired molecular pathway during perinatal asphyxia and TH are the TCA cycle and the osmoregulation system.…”

Section: Introductionmentioning

confidence: 99%

Urinary gas chromatography mass spectrometry metabolomics in asphyxiated newborns undergoing hypothermia: from the birth to the first month of life

Noto¹,

Pomero²,

Mussap³

et al. 2016

Ann. Transl. Med.

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Background: Perinatal asphyxia is a severe clinical condition affecting around four million newborns worldwide.It consists of an impaired gas exchange leading to three biochemical components: hypoxemia, hypercapnia and metabolic acidosis. Methods:The aim of this longitudinal experimental study was to identify the urine metabolome of newborns with perinatal asphyxia and to follow changes in urine metabolic profile over time. Twelve babies with perinatal asphyxia were included in this study; three babies died on the eighth day of life. Total-body cooling for 72 hours was carried out in all the newborns. Urine samples were collected in each baby at birth, after 48 hours during hypothermia, after the end of the therapeutic treatment (72 hours), after 1 week of life, and finally after 1 month of life. Urine metabolome at birth was considered the reference against which to compare metabolic profiles in subsequent samples. Quantitative metabolic profiling in urine samples was measured by gas chromatography mass spectrometry (GC-MS). The statistical approach was conducted by using the multivariate analysis by means of principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA). Pathway analysis was also performed. Results:The most important metabolites depicting each time collection point were identified and compared each other. At birth before starting therapeutic hypothermia (TH), urine metabolic profiles of the three babies died after 7 days of life were closely comparable each other and significantly different from those in survivors. Conclusions:In conclusion, a plethora of data have been extracted by comparing the urine metabolome at birth with those observed at each time point collection. The modifications over time in metabolites composition and concentration, mainly originated from the depletion of cellular energy and homeostasis, seems to constitute a fingerprint of perinatal asphyxia.

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Effects of Acute Systematic Hypoxia on Human Urinary Metabolites Using LC-MS-Based Metabolomics

Cited by 22 publications

References 49 publications

Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

Three plasma metabolite signatures for diagnosing high altitude pulmonary edema

Characterizing the plasma metabolome during 14 days of live‐high, train‐low simulated altitude: A metabolomic approach

Urinary gas chromatography mass spectrometry metabolomics in asphyxiated newborns undergoing hypothermia: from the birth to the first month of life

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