Metabolic Pathways and Networks Associated With Tobacco Use in Military Personnel

Jones, Dean P.; Walker, Douglas I.; Uppal, Karan; Rohrbeck, Patricia; Mallon, Timothy M.; Go, Young‐Mi

doi:10.1097/jom.0000000000000763

Cited by 28 publications

(33 citation statements)

References 37 publications

(50 reference statements)

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“…The resulting set of dysregulated pathways (Table 2) showed considerable overlap with results from a prior study that applied metabolomic analysis to adult serum samples from members of the US armed services obtained from the Department of Defense Serum Repository (DoDSR) (Jones et al, 2016). Of note, five of the top nine pathways altered in sera from military personnel categorized as smokers (serum cotinine ≥ 10 ng/mL) versus light or non-smokers (serum cotinine <10 ng/mL) were also disrupted in the amniotic fluid samples from women showing low-level exposure to nicotine (serum cotinine 2–10 ng/mL).…”

Section: Resultsmentioning

confidence: 86%

“…The LC-MS peak of cotinine ( m/z = 177.1014, RT = 174 seconds) was confirmed by comparing m/z and retention time against the cotinine chemical standard run on the C 18 column with MS/MS confirmation (Jones et al, 2016). The corresponding peak from the HILIC column was identified by matched m/z and correlation of intensities with C 18 analyses.…”

Section: Methodsmentioning

confidence: 97%

“…Sample analysis was performed as previously described (Jones et al, 2016; Soltow et al, 2013). Serum samples were analyzed with three technical replicates on a Thermo Scientific LTQ Velos Orbitrap mass spectrometer, coupled with dual liquid chromatography, alternating data collection between HILIC and C 18 columns.…”

Section: Methodsmentioning

confidence: 99%

“…We averaged the non-zero intensities of technical replicates and performed log 2 transformation. Confirmed metabolite identities were based on accurate mass m/z , coelution with authentic standards, and MS/MS criteria (Go, Liang, et al, 2015; Go, Walker, et al, 2015; Jones et al, 2016). To compare the global metabolic profiles of serum and amniotic fluid, we generated additional tentative matches for all m/z features to metabolites in the Kyoto Encyclopedia for Genes and Genomes (KEGG) database (Kanehisa & Goto, 2000) using xMSannotator (Uppal, Walker, & Jones, 2016), restricting matches to adducts M+H and M+Na with mass error within ±10 ppm.…”

Section: Methodsmentioning

confidence: 99%

“…Subjects were classified according to serum cotinine thresholds of 2 ng/mL, indicative of low-level exposure from light smoking or secondhand smoke, and 10 ng/mL, indicative of smoking (Hanke, Sobala, & Kalinka, 2004; Jones et al, 2016; Misra & Nguyen, 1999). Fifteen samples with cotinine levels close to the defined cutoffs that fell into different exposure groups between chromatography columns were excluded from the primary analysis.…”

Section: Methodsmentioning

confidence: 99%

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Low-level maternal exposure to nicotine associates with significant metabolic perturbations in second-trimester amniotic fluid

Fischer

Lili

et al. 2017

Environment International

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Decades of public health research have documented that smoking in pregnancy poses significant health risks to both mother and child. More recent studies have shown that even passive maternal exposure to secondhand smoke associates with negative birth outcomes. However, the mechanisms linking exposure to outcomes have remained obscure. As a first step toward defining the metabolic consequence of low-level nicotine exposure on fetal development, we conducted an untargeted metabolomic analysis of 81 paired samples of maternal serum and amniotic fluid collected from karyotypically normal pregnancies in the second trimester. By comparing the m/z and retention times of our mass spectral features with confirmed standards, we identified cotinine, a nicotine derivative, and used the calculated cotinine concentrations to classify our maternal serum samples into exposure groups using previously defined cut-offs. We found that cotinine levels consistent with low-level maternal exposure to nicotine associated with distinct metabolic perturbations, particularly in amniotic fluid. In fact, the metabolic effects in amniotic fluid of ostensibly low-level exposed mothers showed greater overlap with perturbations previously observed in the sera of adult smokers than did the perturbations observed in the corresponding maternal sera. Dysregulated fetal pathways included aspartate and asparagine metabolism, pyrimidine metabolism, and metabolism of other amino acids. We also observed a strong negative association between level of maternal serum cotinine and acetylated polyamines in the amniotic fluid. Combined, these results confirm that low-level maternal nicotine exposure, indicated by a maternal serum cotinine level of 2–10 ng/mL, is associated with striking metabolic consequences in the fetal compartment, and that the affected pathways overlap those perturbed in the sera of adult smokers.

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Section: Resultsmentioning

confidence: 86%

Section: Methodsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Low-level maternal exposure to nicotine associates with significant metabolic perturbations in second-trimester amniotic fluid

Fischer

Lili

et al. 2017

Environment International

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Metabolic perturbations in classic galactosemia beyond the Leloir pathway: Insights from an untargeted metabolomic study

Fischer

Frederick

Tran

et al. 2019

J of Inher Metab Disea

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Classic galactosemia (CG) is an autosomal recessive disorder that impacts close to 1/50000 live births in the United States, with varying prevalence in other countries. Following exposure to milk, which contains high levels of galactose, affected infants may experience rapid onset and progression of potentially lethal symptoms. With the benefit of early diagnosis, generally by newborn screening, and immediate and lifelong dietary restriction of galactose, the acute sequelae of disease can be prevented or resolved. However, long‐term complications are common, and despite many decades of research, the bases of these complications remain unexplained. As a step toward defining the underlying pathophysiology of long‐term outcomes in CG, we applied an untargeted metabolomic approach with mass spectrometry and dual liquid chromatography, comparing thousands of small molecules in plasma samples from 183 patients and 31 controls. All patients were on galactose‐restricted diets. Using both univariate and multivariate statistical methods, we identified 252 differentially abundant features from anion exchange chromatography and 167 differentially abundant features from C18 chromatography. Mapping these discriminatory features to putative metabolites and biochemical pathways revealed 14 significantly perturbed pathways; these included multiple redox, amino acid, and mitochondrial pathways, among others. Finally, we tested whether any discriminatory features also distinguished cases with mild vs more severe long‐term outcomes and found multiple candidates, of which one achieved false discovery rate‐adjusted q < 0.1. These results extend substantially from prior targeted studies of metabolic perturbation in CG and offer a new approach to identifying candidate modifiers and targets for intervention.

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Toxicity testing in the 21st century: progress in the past decade and future perspectives

Andersen²,

et al. 2019

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Metabolic Pathways and Networks Associated With Tobacco Use in Military Personnel

Cited by 28 publications

References 37 publications

Low-level maternal exposure to nicotine associates with significant metabolic perturbations in second-trimester amniotic fluid

Low-level maternal exposure to nicotine associates with significant metabolic perturbations in second-trimester amniotic fluid

Metabolic perturbations in classic galactosemia beyond the Leloir pathway: Insights from an untargeted metabolomic study

Toxicity testing in the 21st century: progress in the past decade and future perspectives

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