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Metabolome-Wide Association Study of the Relationship Between Habitual Physical Activity and Plasma Metabolite Levels.

ABSTRACT: We identified plasma metabolites associated with habitual physical activity among 5,197 US participants from the Nurses' Health Study (NHS), Nurses' Health Study II (NHS II), and the Health Professionals Follow-up Study (HPFS). Physical activity was assessed every 2-4 years via self-report questionnaires. Blood was collected in the NHS in 1989-1990, in NHS II during 1996-1999, and in the HPFS during 1993-1995. Metabolic profiling was conducted by liquid chromatography-mass spectrometry. Our study included 337 known metabolites, with 256 of them classified as lipids. We corrected for multiple testing by controlling the tail probability of the proportion of false positives (TPPFP) and accounted for correlated tests using bootstrapping. Physical activity was significantly associated with 20 metabolites after correction for multiple testing (TPPFP < 0.05), and positive associations were found for most of the metabolites, including 2 amino acids (citrulline and glycine), 4 cholesteryl esters (C18:2, C18:1, C16:0, C18:3), 8 phosphocholines (PCs) (C36:4 PC-A, C34:3 PC plasmalogen, C36:3 PC plasmalogen, C34:2 PC plasmalogen, C36:2 PC) and lysophosphatidylcholines (C18:2, C20:5, C18:1), and 3 phosphatidylethanolamines (PEs) (C38:3 PE plasmalogen) and lysophosphatidylethanolamines (C18:2, C18:1). We independently replicated the 20 metabolites among 2,305 women in the Women's Health Initiative using 1993 data, and half of the metabolites were replicated. Our study may help identify biomarkers of physical activity and provide insight into biological mechanisms underlying the beneficial effect of being physically active on cardiometabolic health.

SUBMITTER: Ding M

PROVIDER: S-EPMC6825824 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Metabolome-Wide Association Study of the Relationship Between Habitual Physical Activity and Plasma Metabolite Levels.

Ding Ming M Zeleznik Oana A OA Guasch-Ferre Marta M Hu Jie J Lasky-Su Jessica J Lee I-Min IM Jackson Rebecca D RD Shadyab Aladdin H AH LaMonte Michael J MJ Clish Clary C Eliassen A Heather AH Sacks Frank F Willett Walter C WC Hu Frank B FB Rexrode Kathryn M KM Kraft Peter P

American journal of epidemiology 20191101 11

We identified plasma metabolites associated with habitual physical activity among 5,197 US participants from the Nurses' Health Study (NHS), Nurses' Health Study II (NHS II), and the Health Professionals Follow-up Study (HPFS). Physical activity was assessed every 2-4 years via self-report questionnaires. Blood was collected in the NHS in 1989-1990, in NHS II during 1996-1999, and in the HPFS during 1993-1995. Metabolic profiling was conducted by liquid chromatography-mass spectrometry. Our stud ...[more]

PMID: 31364705

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Project description:IntroductionOrganophosphate (OP) insecticides, including chlorpyrifos, have been linked with numerous harmful health effects on maternal and child health. Limited data are available on the biological mechanisms and endogenous pathways underlying the toxicity of chlorpyrifos exposures on pregnancy and birth outcomes. In this study, we measured a urinary chlorpyrifos metabolite and used high-resolution metabolomics (HRM) to identify biological perturbations associated with chlorpyrifos exposure among pregnant women in Thailand, who are disparately exposed to high levels of OP insecticides.MethodsThis study included 50 participants from the Study of Asian Women and their Offspring's Development and Environmental Exposures (SAWASDEE). We used liquid chromatography-high resolution mass spectrometry to conduct metabolic profiling on first trimester serum samples collected from participants to evaluate metabolic perturbations in relation to chlorpyrifos exposures. We measured 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of chlorpyrifos and chlorpyrifos-methyl, in first trimester urine samples to assess the levels of exposures. Following an untargeted metabolome-wide association study workflow, we used generalized linear models, pathway enrichment analyses, and chemical annotation to identify significant metabolites and pathways associated with urinary TCPy levels.ResultsIn the 50 SAWASDEE participants, the median urinary TCPy level was 4.36 μg TCPy/g creatinine. In total, 691 unique metabolic features were found significantly associated with TCPy levels (p < 0.05) after controlling for confounding factors. Pathway analysis of metabolic features associated with TCPy indicated perturbations in 24 metabolic pathways, most closely linked to the production of reactive oxygen species and cellular damage. These pathways include tryptophan metabolism, fatty acid oxidation and peroxisome metabolism, cytochromes P450 metabolism, glutathione metabolism, and vitamin B3 metabolism. We confirmed the chemical identities of 25 metabolites associated with TCPy levels, including glutathione, cystine, arachidic acid, itaconate, and nicotinamide adenine dinucleotide.DiscussionThe metabolic perturbations associated with TCPy levels were related to oxidative stress, cellular damage and repair, and systemic inflammation, which could ultimately contribute to health outcomes, including neurodevelopmental deficits in the child. These findings support the future development of sensitive biomarkers to investigate the metabolic underpinnings related to pesticide exposure during pregnancy and to understand its link to adverse outcomes in children.

Project description:BackgroundRegular physical activity elicits many health benefits. However, the underlying molecular mechanisms through which physical activity influences overall health are less understood. Untargeted metabolomics enables system-wide mapping of molecular perturbations which may lend insights into physiological responses to regular physical activity. In this study, we investigated the associations of habitual physical activity with plasma and urine metabolome in adolescents and young adults.MethodsThis cross-sectional study included participants from the DONALD (DOrtmund Nutritional and Anthropometric Longitudinally Designed) study with plasma samples n = 365 (median age: 18.4 (18.1, 25.0) years, 58% females) and 24 h urine samples n = 215 (median age: 18.1 (17.1, 18.2) years, 51% females). Habitual physical activity was assessed using a validated Adolescent Physical Activity Recall Questionnaire. Plasma and urine metabolite concentrations were determined using ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) methods. In a sex-stratified analysis, we conducted principal component analysis (PCA) to reduce the dimensionality of metabolite data and to create metabolite patterns. Multivariable linear regression models were then applied to assess the associations between self-reported physical activity (metabolic equivalent of task (MET)-hours per week) with single metabolites and metabolite patterns, adjusted for potential confounders and controlling the false discovery rate (FDR) at 5% for each set of regressions.ResultsHabitual physical activity was positively associated with the "lipid, amino acids and xenometabolite" pattern in the plasma samples of male participants only (β = 1.02; 95% CI: 1.01, 1.04, p = 0.001, adjusted p = 0.042). In both sexes, no association of physical activity with single metabolites in plasma and urine and metabolite patterns in urine was found (all adjusted p > 0.05).ConclusionsOur explorative study suggests that habitual physical activity is associated with alterations of a group of metabolites reflected in the plasma metabolite pattern in males. These perturbations may lend insights into some of underlying mechanisms that modulate effects of physical activity.

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Metabolome-Wide Association Study of the Relationship Between Habitual Physical Activity and Plasma Metabolite Levels.

Publications

Metabolome-Wide Association Study of the Relationship Between Habitual Physical Activity and Plasma Metabolite Levels.

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