Molecular phenotyping of a UK population: defining the human serum metabolome

Dunn, Warwick B.; Lin, Wen; Broadhurst, David; Begley, Paul; Brown, Marie; Zelena, Eva; Vaughan, Andrew A.; Halsall, Antony; Harding, Nadine; Knowles, Joshua; Francis-McIntyre, Sue; Tseng, Andy; Ellis, David I.; O’Hagan, Steve; Aarons, Gill; Benjamin, Boben; Chew-Graham, Stephen; Moseley, Carly; Potter, Paula W.; Winder, Catherine; Potts, Catherine; Thornton, Paula; McWhirter, Catriona; Zubair, Maria; Pan, Martin; Burns, Alistair; Cruickshank, J.; Jayson, Gordon C; Purandare, Nitin; Wu, Frederick C. W.; Finn, Joe D.; Haselden, John N.; Nicholls, Andrew W.; Wilson, Ian D.; Goodacre, Royston; Kell, Douglas B.

doi:10.1007/s11306-014-0707-1

Cited by 220 publications

(213 citation statements)

References 70 publications

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“…At least 600 samples has been suggested as necessary for serum metabolomics studies. 69 The studies in this thesis are much smaller than this, representing 10, 26 and 24 preeclampsia cases in papers I, II and III respectively.…”

Section: Multivariate Analysesmentioning

confidence: 90%

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Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics

et al. 2015

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Section: Multivariate Analysesmentioning

confidence: 90%

“…69 71 Metabolomic studies of human subjects have investigated bio uids and tissues such as urine, blood serum or plasma, cancer tissue, ocular tissue, and even hair. 69, 72 74 Metabolomics has been employed to assess risk, diagnosis and subgrouping of CVD, diabetes and cancer, amongst others.…”

Section: The Human Metabolomementioning

confidence: 99%

Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics

et al. 2015

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“…Using stored (at 280°C) 24-hour urine collection samples from the final week (i.e., week 5) of each sodium condition, we performed a LC-MS/MS-based analysis of 289 metabolites. Storage at 280°C is the recommended condition for long-term LC-MS/MS-based metabolomic analyses (17) and samples have been shown to be stable across time and freeze thaw cycles with this storage method (18). These technologies are well established in our laboratory (19)(20)(21)(22) and utilize a positive/negative ion switching, targeted mass spectrometry-based metabolomics platform on an AB Sciex 5500 QTRAP system (AB Sciex, Concord, ON, Canada) that was established by Yuan et al (23) and further extended and improved within our laboratory.…”

Section: Urine Metabolomicsmentioning

confidence: 99%

Effect of Dietary Sodium Restriction on Human Urinary Metabolomic Profiles

Jablonski

Klawitter

Chonchol

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Metabolomics is a relatively new field of "-omics" research, focusing on highthroughput identification of small molecular weight metabolites. Diet has both acute and chronic effects on metabolic profiles; however, alterations in response to dietary sodium restriction (DSR) are completely unknown. The goal of this study was to explore changes in urine metabolites in response to DSR, as well as their association with previously reported improvements in vascular function with DSR.Design, setting, participants, & measurements Using stored urine samples from a 10-week randomized placebo-controlled crossover study of DSR in 17 middle-aged/older adults (six men and 11 women; mean age 6268 years) who had moderately elevated systolic BP (130-159 mmHg) and were otherwise healthy, a liquid chromatography/mass spectrometry-based analysis of 289 metabolites was performed. This study identified metabolites that were significantly altered between the typical (153629 mmol/d) and low (70629 mmol/d) sodium conditions, as well as their baseline (typical sodium) association with responsiveness to previously reported improvements in vascular endothelial function (brachial artery flow-mediated dilation) and large elastic artery stiffness (aortic pulse wave velocity).Results Of the 289 metabolites surveyed, 10 were significantly altered (nine were upregulated and one was downregulated) during the low sodium condition, and eight of these exceeded our prespecified clinically significant threshold of a .40% change. These metabolites were involved in biologic pathways broadly related to cardiovascular risk, nitric oxide production, oxidative stress, osmotic regulation, and metabolism. One metabolite, serine, was independently (positively) associated with previously reported improvements in the primary vascular outcome of brachial artery flow-mediated dilation.Conclusions This proof-of-concept study provides the first evidence that DSR is a stimulus that induces significant changes in urinary metabolomic profiles. Moreover, serine was independently associated with corresponding changes in vascular endothelial function after DSR. Larger follow-up studies will be required to confirm and further elucidate the metabolic pathways that are altered in response to DSR.

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“…are now available (12)(13)(14)(15)(16). These studies are useful to understand disease mechanisms and to identify diagnostic markers for diseases, such as diabetes (17).…”

mentioning

confidence: 99%

Individual variability in human blood metabolites identifies age-related differences

Chaleckis

Murakami

Takada

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

312

327

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Metabolites present in human blood document individual physiological states influenced by genetic, epigenetic, and lifestyle factors. Using high-resolution liquid chromatography-mass spectrometry (LC-MS), we performed nontargeted, quantitative metabolomics analysis in blood of 15 young (29 ± 4 y of age) and 15 elderly (81 ± 7 y of age) individuals. Coefficients of variation (CV = SD/mean) were obtained for 126 blood metabolites of all 30 donors. Fiftyfive RBC-enriched metabolites, for which metabolomics studies have been scarce, are highlighted here. We found 14 blood compounds that show remarkable age-related increases or decreases; they include 1,5-anhydroglucitol, dimethyl-guanosine, acetyl-carnosine, carnosine, ophthalmic acid, UDP-acetyl-glucosamine, N-acetyl-arginine, N 6 -acetyl-lysine, pantothenate, citrulline, leucine, isoleucine, NAD + , and NADP + . Six of them are RBC-enriched, suggesting that RBC metabolomics is highly valuable for human aging research. Age differences are partly explained by a decrease in antioxidant production or increasing inefficiency of urea metabolism among the elderly. Pearson's coefficients demonstrated that some age-related compounds are correlated, suggesting that aging affects them concomitantly. Although our CV values are mostly consistent with those CVs previously published, we here report previously unidentified CVs of 51 blood compounds. Compounds having moderate to high CV values (0.4-2.5) are often modified. Compounds having low CV values, such as ATP and glutathione, may be related to various diseases because their concentrations are strictly controlled, and changes in them would compromise health. Thus, human blood is a rich source of information about individual metabolic differences. H uman blood metabolites have been well-investigated to determine their abundance and biological significance, and for their potential use as diagnostic markers. For medical diagnosis, noncellular metabolites from plasma or serum are mostly commonly used due to the simplicity in collecting and examining them. Although mature human red blood cells (RBCs) lack nuclei and cellular organelles (1), RBCs use glycolysis for ATP production, maintain redox homeostasis, and osmoregulate (2). Their active metabolism supports cellular homeostasis and ensures lifespans of ∼4 mo (3). Their metabolites may reflect health status or environmental stresses differently than do metabolites of plasma. Because RBCs occupy about half the total blood volume (∼5 L), their metabolite profiles, which have scarcely been investigated, seemed worthy of investigation.Metabolomics is a branch of chemical biology that profiles metabolites in cells and organisms, using techniques such as liquid chromatography (LC)-mass spectrometry (MS). It usually deals with molecules <1.5 kDa and is an important tool for studying metabolic regulation in combination with other comprehensive analyses, such as proteomics and transcriptomics. Recently, we reported that, among 133 compounds identified in human blood, 101 are also found...

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Molecular phenotyping of a UK population: defining the human serum metabolome

Cited by 220 publications

References 70 publications

Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics

Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics

Effect of Dietary Sodium Restriction on Human Urinary Metabolomic Profiles

Individual variability in human blood metabolites identifies age-related differences

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