Summary of Study ST001406
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
| Study ID | ST001406 |
| Study Title | Environmental chemical burden in metabolic tissues and systemic biological pathways in adolescent bariatric surgery patients: A pilot untargeted metabolomic approach (part-II) |
| 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 | 2020-06-19 |
| Num Groups | 4 |
| 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 | GC-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: | SU001480 |
| 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 | Tissue Type |
|---|---|---|
| SA114151 | POTR_11_sAT | INTRA-ABDOMINAL ADIPOSE TISSUE |
| SA114152 | POTR_12_sAT | INTRA-ABDOMINAL ADIPOSE TISSUE |
| SA114153 | POTR_03_sAT | INTRA-ABDOMINAL ADIPOSE TISSUE |
| SA114154 | POTR_02_sAT | INTRA-ABDOMINAL ADIPOSE TISSUE |
| SA114155 | POTR_09_sAT | INTRA-ABDOMINAL ADIPOSE TISSUE |
| SA114156 | POTR_10_sAT | INTRA-ABDOMINAL ADIPOSE TISSUE |
| SA114157 | POTR_08_sAT | INTRA-ABDOMINAL ADIPOSE TISSUE |
| SA114158 | POTR_04_sAT | INTRA-ABDOMINAL ADIPOSE TISSUE |
| SA114159 | POTR_06_sAT | INTRA-ABDOMINAL ADIPOSE TISSUE |
| SA114160 | POTR_05_sAT | INTRA-ABDOMINAL ADIPOSE TISSUE |
| SA114161 | POTR_07_sAT | INTRA-ABDOMINAL ADIPOSE TISSUE |
| SA114162 | POTR_07_Liver | LIVER |
| SA114163 | POTR_06_Liver | LIVER |
| SA114164 | POTR_04_Liver | LIVER |
| SA114165 | POTR_02_Liver | LIVER |
| SA114166 | POTR_05_Liver | LIVER |
| SA114167 | POTR_03_Liver | LIVER |
| SA114168 | POTR_12_Liver | LIVER |
| SA114169 | POTR_11_Liver | LIVER |
| SA114170 | POTR_10_Liver | LIVER |
| SA114171 | POTR_09_Liver | LIVER |
| SA114172 | POTR_08_Liver | LIVER |
| SA114173 | POTR_07_vAT | SUBCUTANEOUS ADIPOSE TISSUE |
| SA114174 | POTR_05_vAT | SUBCUTANEOUS ADIPOSE TISSUE |
| SA114175 | POTR_04_vAT | SUBCUTANEOUS ADIPOSE TISSUE |
| SA114176 | POTR_03_vAT | SUBCUTANEOUS ADIPOSE TISSUE |
| SA114177 | POTR_02_vAT | SUBCUTANEOUS ADIPOSE TISSUE |
| SA114178 | POTR_06_vAT | SUBCUTANEOUS ADIPOSE TISSUE |
| SA114179 | POTR_08_vAT | SUBCUTANEOUS ADIPOSE TISSUE |
| SA114180 | POTR_11_vAT | SUBCUTANEOUS ADIPOSE TISSUE |
| SA114181 | POTR_10_vAT | SUBCUTANEOUS ADIPOSE TISSUE |
| SA114182 | POTR_09_vAT | SUBCUTANEOUS ADIPOSE TISSUE |
| SA114183 | POTR_12_vAT | SUBCUTANEOUS ADIPOSE TISSUE |
| Showing results 1 to 33 of 33 |
Collection:
| Collection ID: | CO001475 |
| 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: | Adipose tissue |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR001495 |
| 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: | SP001488 |
| Sampleprep Summary: | Tissue POPs concentrations were measured in vAT, sAT and liver tissues collected during surgery. All tissue samples were prepared in batches of 11 study samples and 3 method blanks using a modified version of the QuECHERS method described by (Zamariola et al. 2017). Briefly, 0.2-0.5g of tissue was weighed, placed in an amber glass vial and treated with 3.5mL of LC-MS grade water. Each sample was then spiked with 50μL internal standard solution prepared in 2-proponal that was designed to represent environmental chemicals with a range of physiochemical properties to monitor analysis QA/QC, and included 500 ng/mL [13C6]-Anthracene, [13C12]-PCB28, [DIETHYL-D10]-Chlorpyrifos, [13C12]-PCB101, [13C12]-4,4'-DDE, [13C12]-PCB153, [13C12]-PCB180, [13C12]-PBDE47, [13C10]-Mirex, [13C6]-cis-Permethrin, [13C12]-PBDE99 and [13C12]-PBB153. Following addition of the internal standard solution, the sample was then homogenized for 1 min and placed in a sonicating bath for 10 min. The resulting homogenate was transferred to a 50 mL conical tube containing 10mL acetonitrile, 4000mg MgSO4 and1000mg NaCl, and vortexed for 5 min. After centrifuging, a 1.5mL aliquout was transferred to a cleanup tube containing 50 mg primary and secondary amine exchange material (PSA), 50 mg C18 and 150 mg MgSO4, vortex-mixed for 1 min and centrifuged at max speed for 5 min. From the supernatant, a 1 mL aliquot was transferred to a clean, glass tube and dried completely in a vacuum centrifuge operated at 35°C. The residue was then resuspended in 50μL isooctane and transferred to a GC vial containing a low volume insert and capped with a Teflon lined cap until analysis. |
| Sampleprep Protocol ID: | douglas_walker_Protocol_for_adipose_tissue_exposomics_v3_08Mar2018.pdf |
| Sampleprep Protocol Filename: | douglas_walker_Protocol_for_adipose_tissue_exposomics_v3_08Mar2018.pdf |
| Processing Storage Conditions: | Room temperature |
Combined analysis:
| Analysis ID | AN002349 |
|---|---|
| Analysis type | MS |
| Chromatography type | GC |
| Chromatography system | Thermo Trace 1310 |
| Column | Agilent DB5-MS (30m x 0.25mm, 0.25um) |
| MS Type | EI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Q Exactive GC Orbitrap GC-MS/MS |
| Ion Mode | POSITIVE |
| Units | pg/g |
Chromatography:
| Chromatography ID: | CH001721 |
| Chromatography Summary: | Tissue extracts were analyzed using a Thermo Scientific 1310 gas chromatograph connected to a Q Exactive GC Orbitrap GC-MS/MS ultra-high-resolution mass spectrometer and Triplus RSH autosampler. A 2 µL aliquot of extract was injected into an inlet maintained at 250ºC in pulsed split-less mode. The analytes were separated on an Agilent DB-5MSUI capillary column (30m length × 0.25mm inner diameter × 0.25µm film thickness) using high purity helium (99.999% purity) as the carrier gas at a constant flow rate of 1 mL/min. The oven temperature program consisted of an initial temperature of 100ºC for 1 min, increased to 180ºC at 25ºC/min; followed by a temperature ramp to 215ºC at 5ºC/min, and finally increased to 300ºC at 25ºC/min and held for 10 min, resulting in a total run time of 26.6 min. |
| Instrument Name: | Thermo Trace 1310 |
| Column Name: | Agilent DB5-MS (30m x 0.25mm, 0.25um) |
| Flow Rate: | 1 mL/min |
| Injection Temperature: | 250C |
| Internal Standard: | [13C6]-Anthracene, [13C12]-PCB28, [DIETHYL-D10]-Chlorpyrifos, [13C12]-PCB101, [13C12]-4,4'-DDE, [13C12]-PCB153, [13C12]-PCB180, [13C12]-PBDE47, [13C10]-Mirex, [13C6]-cis-Permethrin, [13C12]-PBDE99 and [13C12]-PBB153 |
| Sample Injection: | 2 uL |
| Analytical Time: | 26.6 |
| Oven Temperature: | The oven temperature program consisted of an initial temperature of 100ºC for 1 min, increased to 180ºC at 25ºC/min; followed by a temperature ramp to 215ºC at 5ºC/min, and finally increased to 300ºC at 25ºC/min and held for 10 min |
| Transferline Temperature: | 280 |
| Sample Syringe Size: | 10uL |
| Chromatography Type: | GC |
MS:
| MS ID: | MS002191 |
| Analysis ID: | AN002349 |
| Instrument Name: | Thermo Q Exactive GC Orbitrap GC-MS/MS |
| Instrument Type: | Orbitrap |
| MS Type: | EI |
| MS Comments: | Targeted peak assignment and integration was completed using TraceFinder |
| Ion Mode: | POSITIVE |
| Ion Source Temperature: | 250C |
| Ionization: | Postive |
| Ionization Energy: | -70eV |
