Summary of Study ST001407
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000963. The data can be accessed directly via it's Project DOI: 10.21228/M86X2T This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST001407 |
| Study Title | Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach |
| Study Type | Subcutaneous adipose tissue (AT); Visceral AT; Liver Tissue; Plasma |
| Study Summary | Background: Advances in untargeted metabolomic technologies have great potential for insight into adverse metabolic effects underlying exposure to environmental chemicals. However, important challenges need to be addressed, including how biological response corresponds to the environmental chemical burden in different target tissues. Aim: We performed a pilot study using state-of-the-art ultra-high-resolution mass spectrometry (UHRMS) to characterize the burden of lipophilic persistent organic pollutants (POPs) in metabolic tissues and associated alterations in the plasma metabolome. Methods: We studied 11 adolescents with severe obesity at the time of bariatric surgery. We measured 18 POPs that can act as endocrine and metabolic disruptors (i.e. 2 dioxins, 11 organochlorine compounds [OCs] and 5 polybrominated diphenyl ethers [PBDEs]) in visceral and subcutaneous abdominal adipose tissue (vAT and sAT), and liver samples using gas chromatography with UHRMS. Biological pathways were evaluated by measuring the plasma metabolome using high-resolution metabolomics. Network and pathway enrichment analysis assessed correlations between the tissue-specific burden of three frequently detected POPs (i.e. p,p’-dichlorodiphenyldichloroethene [DDE], hexachlorobenzene [HCB] and PBDE-47) and plasma metabolic pathways. Results: Concentrations of 4 OCs and 3 PBDEs were quantifiable in at least one metabolic tissue for >80% of participants. All POPs had the highest median concentrations in adipose tissue, especially sAT, except for PBDE-154, which had comparable average concentrations across all tissues. Pathway analysis showed high correlations between tissue-specific POPs and metabolic alterations in pathways of amino acid metabolism, lipid and fatty acid metabolism, and carbohydrate metabolism. Conclusions: Most of the measured POPs appear to accumulate preferentially in adipose tissue compared to liver. Findings of plasma metabolic pathways potentially associated with tissue-specific POPs concentrations merit further investigation in larger populations. |
| Institute | Icahn School of Medicine at Mount Sinai |
| Department | Environmental Medicine and Public Health |
| Laboratory | High Resolution Exposomics Research Group |
| Last Name | Walker |
| First Name | Doug |
| Address | One Gustave L. Levy Place, Box 1057, New York, NY 10029 |
| douglas.walker@mssm.edu | |
| Phone | 212-241-9891 |
| Submit Date | 2020-06-22 |
| Num Groups | 1 |
| Total Subjects | 11 |
| Num Males | 1 |
| Num Females | 10 |
| Study Comments | Upload #1: Visceral and subcutaneous abdominal adipose tissue, liver tissue. Plasma metabolomics are in upload #2 |
| Publications | Valvi D, Walker DI, Inge T, Bartell SM, Jenkins T, Helmrath M, Ziegler TR, La Merrill MA, Eckel SP, Conti D, Liang Y, Jones DP, McConnell R, Chatzi L. (2020). Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach. Environment International. In Press. |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2021-06-19 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR000963 |
| Project DOI: | doi: 10.21228/M86X2T |
| Project Title: | Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach |
| Project Type: | Pilot Study |
| Project Summary: | Background: Advances in untargeted metabolomic technologies have great potential for insight into adverse metabolic effects underlying exposure to environmental chemicals. However, important challenges need to be addressed, including how biological response corresponds to the environmental chemical burden in different target tissues. Aim: We performed a pilot study using state-of-the-art ultra-high-resolution mass spectrometry (UHRMS) to characterize the burden of lipophilic persistent organic pollutants (POPs) in metabolic tissues and associated alterations in the plasma metabolome. Methods: We studied 11 adolescents with severe obesity at the time of bariatric surgery. We measured 18 POPs that can act as endocrine and metabolic disruptors (i.e. 2 dioxins, 11 organochlorine compounds [OCs] and 5 polybrominated diphenyl ethers [PBDEs]) in visceral and subcutaneous abdominal adipose tissue (vAT and sAT), and liver samples using gas chromatography with UHRMS. Biological pathways were evaluated by measuring the plasma metabolome using high-resolution metabolomics. Network and pathway enrichment analysis assessed correlations between the tissue-specific burden of three frequently detected POPs (i.e. p,p’-dichlorodiphenyldichloroethene [DDE], hexachlorobenzene [HCB] and PBDE-47) and plasma metabolic pathways. Results: Concentrations of 4 OCs and 3 PBDEs were quantifiable in at least one metabolic tissue for >80% of participants. All POPs had the highest median concentrations in adipose tissue, especially sAT, except for PBDE-154, which had comparable average concentrations across all tissues. Pathway analysis showed high correlations between tissue-specific POPs and metabolic alterations in pathways of amino acid metabolism, lipid and fatty acid metabolism, and carbohydrate metabolism. Conclusions: Most of the measured POPs appear to accumulate preferentially in adipose tissue compared to liver. Findings of plasma metabolic pathways potentially associated with tissue-specific POPs concentrations merit further investigation in larger populations. Keywords: persistent organic pollutants, adipose tissue, liver, bariatric surgery, exposome, high-resolution metabolomics |
| Institute: | Icahn School of Medicine at Mount Sinai |
| Department: | Environmental Medicine and Public Health |
| Laboratory: | High Resolution Exposomics Research Group |
| Last Name: | Walker |
| First Name: | Douglas |
| Address: | One Gustave L. Levy Place, Box 1057, New York, NY 10029 |
| Email: | douglas.walker@mssm.edu |
| Phone: | 212-241-9891 |
| Funding Source: | NIEHS: R21ES028903, R21ES029328, R21ES029681, R01ES029944, R01ES030364, U2CES026561, U2CES030163, P30ES023515, P30 ES019776, P30ES007048, P01ES022845, R01ES024946; EPA: RD-83544101 |
| Publications: | Valvi D, Walker DI, Inge T, Bartell SM, Jenkins T, Helmrath M, Ziegler TR, La Merrill MA, Eckel SP, Conti D, Liang Y, Jones DP, McConnell R, Chatzi L. (2020). Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach. Environment International. In Press. |
| Contributors: | Valvi D, Walker DI, Inge T, Bartell SM, Jenkins T, Helmrath M, Ziegler TR, La Merrill MA, Eckel SP, Conti D, Liang Y, Jones DP, McConnell R, Chatzi L |
Subject:
| Subject ID: | SU001481 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Age Or Age Range: | 11-20 years |
| Gender: | Male and female |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Description |
|---|---|---|
| SA114184 | chearplasma_1c | CHEAR plasma pool |
| SA114185 | chearplasma_1d | CHEAR plasma pool |
| SA114186 | chearplasma_1b | CHEAR plasma pool |
| SA114187 | chearplasma_1a | CHEAR plasma pool |
| SA114188 | NIST_1958_2 | NIST 1958 |
| SA114189 | NIST_1958_1 | NIST 1958 |
| SA114190 | POTR_02_Plasma | POTR_02 |
| SA114191 | POTR_03_Plasma | POTR_03 |
| SA114192 | POTR_04_Plasma | POTR_04 |
| SA114193 | POTR_05_Plasma | POTR_05 |
| SA114194 | POTR_06_Plasma | POTR_06 |
| SA114195 | POTR_07_Plasma | POTR_07 |
| SA114196 | POTR_08_Plasma | POTR_08 |
| SA114197 | POTR_09_Plasma | POTR_09 |
| SA114198 | POTR_10_Plasma | POTR_10 |
| SA114199 | POTR_11_Plasma | POTR_11 |
| SA114200 | POTR_12_Plasma | POTR_12 |
| SA114201 | q3June2014_1a | Q-Standard plasma pool |
| SA114202 | q3June2014_1b | Q-Standard plasma pool |
| SA114203 | q3June2014_1d | Q-Standard plasma pool |
| SA114204 | q3June2014_1c | Q-Standard plasma pool |
| Showing results 1 to 21 of 21 |
Collection:
| Collection ID: | CO001476 |
| Collection Summary: | Eleven adolescents 12–20 years of age undergoing bariatric surgery at Cincinnati Children’s Hospital between 2006 and 2012 were offered enrollment in a prospective biospecimen repository protocol (Pediatric Obesity Tissue Repository [POTR]). Sample recruitment and other POTR features have been reported previously (Davidson et al. 2017). Intraoperatively, visceral adipose tissue (vAT) samples from the omentum, abdominal subcutaneous AT (sAT), and liver samples were obtained by the surgeon and processed immediately in an area adjacent to the operating room. All samples were snap-frozen in liquid nitrogen, then stored at −80°C. Plasma was collected pre-operatively after overnight fasting and stored at -80°C. Written informed consent was obtained from participants equal to or above 18 years old or from the parent or guardian if participants were less than 18 years old. The study was approved by the Institutional Review Board at Cincinnati Children’s Hospital. |
| Sample Type: | Blood (plasma) |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR001496 |
| Treatment Summary: | The objective of the observational study was to evaluate the relationship between adipose and liver tissue POPs and the plasma metabolome. All participants underwent bariatric surgery at the time of tissue collection. No other treatment or intervention was evaluated. |
Sample Preparation:
| Sampleprep ID: | SP001489 |
| Sampleprep Summary: | Samples are prepared for metabolomics analysis using established methods (Johnson et al. (2010). Analyst; Go et al. (2015). Tox Sci). Prior to analysis, plasma aliquots were removed from storage at -80°C and thawed on ice. Each cryotube is then vortexed briefly to ensure homogeneity, and 50 μL transferred to a clean microfuge tube. Immediately after, the plasma is treated with 100 μL of ice-cold LC-MS grade acetonitrile (Sigma Aldrich) containing 2.5 μL of internal standard solution with eight stable isotopic chemicals selected to cover a range of chemical properties. Following addition of acetonitrile, plasma is then equilibrated for 30 min on ice, upon which precipitated proteins are removed by centrifuge (16.1 ×g at 4°C for 10 min). The resulting supernatant (100 μL) is removed, added to a low volume autosampler vial and maintained at 4°C until analysis (<22 h). |
| Sampleprep Protocol ID: | EmoryUniversity_HRM_SP_082016_01.pdf |
| Sampleprep Protocol Filename: | EmoryUniversity_HRM_SP_082016_01.pdf |
| Processing Storage Conditions: | Room temperature |
Combined analysis:
| Analysis ID | AN002350 | AN002351 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | Reversed phase |
| Chromatography system | Thermo Dionex Ultimate 3000 | Thermo Dionex Ultimate 3000 |
| Column | Waters XBridge BEH Amide XP HILIC (50 x 2.1mm,2.5um) | Higgins endcapped C18 stainless steel (50 x 2.1mm,3um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive HF hybrid Orbitrap | Thermo Q Exactive HF hybrid Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | Peak intensity | Peak intensity |
Chromatography:
| Chromatography ID: | CH001722 |
| Chromatography Summary: | The HILIC column is operated parallel to reverse phase column for simultaneous analytical separation and column flushing through the use of a dual head HPLC pump equipped with 10- port and 6-port switching valves. During operation of HILIC separation method, the MS is operated in positive ion mode and 10 μL of sample is injected onto the HILIC column while the reverse phase column is flushing with wash solution. Flow rate is maintained at 0.35 mL/min until 1.5 min, increased to 0.4 mL/min at 4 min and held for 1 min. Solvent A is 100% LC-MS grade water, solvent B is 100% LC-MS grade acetonitrile and solvent C is 2% formic acid (v/v) in LC-MS grade water. Initial mobile phase conditions are 22.5% A, 75% B, 2.5% C hold for 1.5 min, with linear gradient to 77.5% A, 20% B, 2.5% C at 4 min, hold for 1 min, resulting in a total analytical run time of 5 min. During the flushing phase (reverse phase analytical separation), the HILIC column is equilibrated with a wash solution of 77.5% A, 20% B, 2.5% C. |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Waters XBridge BEH Amide XP HILIC (50 x 2.1mm,2.5um) |
| Column Temperature: | 60 |
| Flow Gradient: | Initial mobile phase conditions are 22.5% A, 75% B, 2.5% C hold for 1.5 min, with linear gradient to 77.5% A, 20% B, 2.5% C at 4 min, hold for 1 min, resulting in a total analytical run time of 5 min. |
| Flow Rate: | 0.35- 0.4 mL/min |
| Internal Standard: | [13C6]-D-glucose, [15N,13C5]- L-methionine, [13C5]-L-glutamic acid, [15N]-L-tyrosine, [3,3-13C2]-cystine, [trimethyl- 13C3]-caffeine, [U-13C5, U-15N2]-L-glutamine |
| Sample Injection: | 10 uL |
| Solvent A: | 100% water(A), 100% acetonitrile(B), 100% water; 2% formic acid(C) |
| Solvent B: | 100% water(A), 100% acetonitrile(B), 100% water; 2% formic acid(C) |
| Analytical Time: | 5 min |
| Chromatography Type: | HILIC |
| Chromatography ID: | CH001723 |
| Chromatography Summary: | The C18 column is operated parallel to the HILIC column for simultaneous analytical separation and column flushing through the use of a dual head HPLC pump equipped with 10-port and 6- port switching valves. During operation of the C18 method, the MS is operated in negative ion mode and 10 μL of sample is injected onto the C18 column while the HILIC column is flushing with wash solution. Flow rate is maintained at 0.4 mL/min until 1.5 min, increased to 0.5 mL/min at 2 min and held for 3 min. Solvent A is 100% LC-MS grade water, solvent B is 100% LC-MS grade acetonitrile and solvent C is 10mM ammonium acetate in LC-MS grade water. Initial mobile phase conditions are 60% A, 35% B, 5% C hold for 0.5 min, with linear gradient to 0% A, 95% B, 5% C at 1.5 min, hold for 3.5 min, resulting in a total analytical run time of 5 min. During the flushing phase (HILIC analytical separation), the C18 column is equilibrated with a wash solution of 0% A, 95% B, 5% C until 2.5 min, followed by an equilibration solution of 60% A, 35% B, 5% C for 2.5 min. |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Higgins endcapped C18 stainless steel (50 x 2.1mm,3um) |
| Column Temperature: | 60 |
| Flow Gradient: | Initial mobile phase conditions are 60% A, 35% B, 5% C hold for 0.5 min, with linear gradient to 0% A, 95% B, 5% C at 1.5 min, hold for 3.5 min, resulting in a total analytical run time of 5 min. |
| Flow Rate: | Flow rate is maintained at 0.4 mL/min until 1.5 min, increased to 0.5 mL/min at 2 min and held for 3 min. |
| Internal Standard: | [13C6]-D-glucose, [15N,13C5]- L-methionine, [13C5]-L-glutamic acid, [15N]-L-tyrosine, [3,3-13C2]-cystine, [trimethyl- 13C3]-caffeine, [U-13C5, U-15N2]-L-glutamine |
| Sample Injection: | 10 uL |
| Solvent A: | 100% water(A), 100% acetonitrile(B), 100%water; 10mM ammonium acetate(C) |
| Solvent B: | 100% water(A), 100% acetonitrile(B), 100%water; 10mM ammonium acetate(C) |
| Analytical Time: | 5 min |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS002192 |
| Analysis ID: | AN002350 |
| Instrument Name: | Thermo Q Exactive HF hybrid Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | The high-resolution mass spectrometer was operated at 120,000 resolution and mass-to-charge ratio (m/z) range 85-1275. Probe temperature, capillary temperature, sweep gas and S-Lens RF levels were maintained at 200°C, 300°C, 1 arbitrary units (AU), and 45, respectively. Additional source settings were optimized for sensitivity using a standard mixture, tune settings for sheath gas, auxiliary gas, sweep gas and spray voltage setting were 45 AU, 25 AU and 3.5 kV, respectively. Maximum C-trap injection times were set at 100 milliseconds and automatic gain control target 1 × 106. During untargeted data acquisition, no exclusion or inclusion masses were selected, and data was acquired in MS1 mode only. Raw data files were then extracted using apLCMS (Yu et al. 2009) at five different peak detection settings that have been separately optimized for detection of a wide range of peak intensities and abundances. Peaks detected during each injection were aligned using a mass tolerance of 5 ppm (parts-per-million) and retention grouping was accomplished using non-parametric density estimation grouping, with a maximum retention time deviation of 30 seconds. The resulting feature tables were merged using xMSanalyzer, which identifies overlapping or unique features detected across the different peak detection parameters, and retains the peak with the lowest replicate CV and non-detects for inclusion in the final feature table (Uppal et al. 2013). All R-scripts for data extraction with apLCMS and data merging with xMSanalyzer are provided in the supplementary material. Uniquely detected ions consisted of m/z, retention time and ion abundance, referred to as m/z features. Prior to data analysis, triplicate m/z features averaged and filtered to remove those with triplicate coefficient of variation (CV) ≥ 100% and non-detected values greater than 10%. |
| Ion Mode: | POSITIVE |
| Capillary Temperature: | 300C |
| Ion Source Temperature: | 200C |
| Ion Spray Voltage: | 3.5kV |
| Ionization: | Postive |
| Mass Accuracy: | 5ppm |
| Source Temperature: | 200C |
| MS ID: | MS002193 |
| Analysis ID: | AN002351 |
| Instrument Name: | Thermo Q Exactive HF hybrid Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | The high-resolution mass spectrometer was operated at 120,000 resolution and mass-to-charge ratio (m/z) range 85-1275. Probe temperature, capillary temperature, sweep gas and S-Lens RF levels were maintained at 200°C, 300°C, 1 arbitrary units (AU), and 45, respectively. Additional source settings were optimized for sensitivity using a standard mixture, tune settings for sheath gas, auxiliary gas, sweep gas and spray voltage setting were 45 AU, 25 AU and 3.5 kV, respectively. Maximum C-trap injection times were set at 100 milliseconds and automatic gain control target 1 × 106. During untargeted data acquisition, no exclusion or inclusion masses were selected, and data was acquired in MS1 mode only. Raw data files were then extracted using apLCMS (Yu et al. 2009) at five different peak detection settings that have been separately optimized for detection of a wide range of peak intensities and abundances. Peaks detected during each injection were aligned using a mass tolerance of 5 ppm (parts-per-million) and retention grouping was accomplished using non-parametric density estimation grouping, with a maximum retention time deviation of 30 seconds. The resulting feature tables were merged using xMSanalyzer, which identifies overlapping or unique features detected across the different peak detection parameters, and retains the peak with the lowest replicate CV and non-detects for inclusion in the final feature table (Uppal et al. 2013). All R-scripts for data extraction with apLCMS and data merging with xMSanalyzer are provided in the supplementary material. Uniquely detected ions consisted of m/z, retention time and ion abundance, referred to as m/z features. Prior to data analysis, triplicate m/z features averaged and filtered to remove those with triplicate coefficient of variation (CV) ≥ 100% and non-detected values greater than 10%. |
| Ion Mode: | NEGATIVE |
| Capillary Temperature: | 300C |
| Ion Source Temperature: | 200C |
| Ion Spray Voltage: | 3.5kV |
| Ionization: | NEgative |
| Mass Accuracy: | 5ppm |
| Source Temperature: | 200C |
