Summary of Study ST004256
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 PR002684. The data can be accessed directly via it's Project DOI: 10.21228/M8QG20 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 | ST004256 |
| Study Title | Central carbon metabolites in Wild Type (WT) and dioxin response element (DRE) mice treated with TCDD |
| Study Summary | 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) reprograms central carbon metabolism by switching pyruvate kinase expression from isoform M1 (Pkm1) to M2 (Pkm2) mediated by aryl hydrocarbon receptor (AhR) binding to a dioxin response element (DRE) located between exon 3 and 4 within the Pkm locus. To further investigate the consequences of Pkm isoform switching in TCDD elicited hepatotoxicity, we examined gene expression in primary hepatocytes isolated from mice with the Pkm locus DRE excised (PkmΔDRE) as well as metabolic changes in WT and PkmΔDRE mice treated with 30 µg/kg TCDD every 4 day for 28 days. While AHR target genes were comparably induced, some genes exhibited divergent expression patterns in PkmΔDREmice compared to wild-types following treatment with TCDD. Notably, antioxidant gene expression was delayed in PkmΔDRE hepatocytes. Metabolomic analysis also revealed differences in glycolytic, TCA cycle and pentose phosphate pathway metabolite levels in TCDD treated WT and PkmΔDRE liver extracts. In addition, amino acid metabolism and serine/glycine synthesis were also elevated, especially in PkmΔDRE. These findings indicate PKM2 induction affects the transcriptional and metabolic coordination of hepatic responses to TCDD. |
| Institute | Michigan State University |
| Last Name | Orlowska |
| First Name | Karina |
| Address | 1129 Farm Lane, Room 248, East Lansing, Michigan, 48824, USA |
| orlowska@msu.edu | |
| Phone | 5178842054 |
| Submit Date | 2025-09-08 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-10-10 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002684 |
| Project DOI: | doi: 10.21228/M8QG20 |
| Project Title: | Central carbon metabolites in Wild Type (WT) and dioxin response element (DRE) mice |
| Project Type: | Targeted MS |
| Project Summary: | Central carbon metabolite changes were assessed in WT and PkmΔDRE mice treated with 30 µg/kg TCDD every 4 day for 28 days. Metabolomic analysis also revealed differences in glycolytic, TCA cycle and pentose phosphate pathway metabolite levels in TCDD treated WT and PkmΔDRE liver extracts. In addition, amino acid metabolism and serine/glycine synthesis were also elevated, especially in PkmΔDRE. These findings indicate PKM2 induction affects the transcriptional and metabolic coordination of hepatic responses to TCDD. |
| Institute: | Michigan State University |
| Last Name: | Orlowska |
| First Name: | Karina |
| Address: | 1129 Farm Lane, Room 248, East Lansing, Michigan, 48824, USA |
| Email: | orlowska@msu.edu |
| Phone: | 5178842054 |
Subject:
| Subject ID: | SU004408 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Gender: | Male |
| Animal Animal Supplier: | Charles Rivers Laboratories |
| Animal Housing: | Innovive Innocage |
| Animal Light Cycle: | 12:12 |
| Animal Feed: | Harlan Teklad 8940, ad libitum |
| Animal Water: | Innovive, ad libitum |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Sample source | Genotype | Treatment |
|---|---|---|---|---|
| SA496767 | DRE_30_5 | Liver | mutant | TCDD |
| SA496768 | DRE_30_4 | Liver | mutant | TCDD |
| SA496769 | DRE_30_3 | Liver | mutant | TCDD |
| SA496770 | DRE_30_2 | Liver | mutant | TCDD |
| SA496771 | DRE_30_1 | Liver | mutant | TCDD |
| SA496772 | DRE_0_2 | Liver | mutant | Vehicle |
| SA496773 | DRE_0_5 | Liver | mutant | Vehicle |
| SA496774 | DRE_0_4 | Liver | mutant | Vehicle |
| SA496775 | DRE_0_3 | Liver | mutant | Vehicle |
| SA496776 | DRE_0_1 | Liver | mutant | Vehicle |
| SA496757 | WT_30_5 | Liver | WT | TCDD |
| SA496758 | WT_30_4 | Liver | WT | TCDD |
| SA496759 | WT_30_3 | Liver | WT | TCDD |
| SA496760 | WT_30_2 | Liver | WT | TCDD |
| SA496761 | WT_30_1 | Liver | WT | TCDD |
| SA496762 | WT_0_2 | Liver | WT | Vehicle |
| SA496763 | WT_0_5 | Liver | WT | Vehicle |
| SA496764 | WT_0_4 | Liver | WT | Vehicle |
| SA496765 | WT_0_3 | Liver | WT | Vehicle |
| SA496766 | WT_0_1 | Liver | WT | Vehicle |
| Showing results 1 to 20 of 20 |
Collection:
| Collection ID: | CO004401 |
| Collection Summary: | Liver Tissue was carefully excised and immediately frozen in liquid nitrogen. |
| Sample Type: | Liver |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR004417 |
| Treatment Summary: | Mice were orally gavaged with 0.1 mL of the test article (30 µg/kg TCDD) in vehicle (sesame oil) every 4 days for 28 days for a total of 7 administrations. First dose was administrated on PND 28. |
| Treatment Compound: | 2,3,7,8-Tetrachlorodibenzo-p-dioxin |
| Treatment Route: | oral gavage |
| Treatment Dose: | 30 microgram per kilogram |
| Treatment Dosevolume: | 0.1 ml |
| Treatment Doseduration: | every 4 days for 28 days |
| Treatment Vehicle: | sesame oil |
| Animal Fasting: | No |
| Animal Endp Euthanasia: | Carbon dioxide asphyxiation |
Sample Preparation:
| Sampleprep ID: | SP004414 |
| Sampleprep Summary: | Frozen liver samples were homogenized (Polytron PT2100, Kinematica) in methanol 500 μL of HPLC grade methanol, 200 μL of HPLC-grade water and 500 μL of HPLC-grade chloroform. Samples are vortexed for 10 minutes, then centrifuged at 4 °C 16,000xg for 15 minutes. The polar layer was then removed and dried under nitrogen gas. Extracted metabolites were then resuspended in 3% methanol containing 10 mM tributylamine (TBA). |
Chromatography:
| Chromatography ID: | CH005379 |
| Chromatography Summary: | Chromatographic separation utilized an Acquity HSS T3 column (1.8 μm particle size, 2.1 mm × 150 mm). A binary solvent system was applied for gradient elution. The mobile phase A consisted of LC/MS-grade water containing 3% LC/MS-grade methanol, 10 mM tributylamine (TBA), and 15 mM acetic acid (pH 5.0 ± 0.05). Mobile phase B was composed of LC/MS-grade methanol (100%). A constant flow rate of 300 μl/min was maintained and the linear gradient employed was as follows: 0–1.5 min 100% A, 1.5–4 min increase from 0 to 20% B, 4–6. min maintain 80% A and 20% B, 6–10.5 min increase from 20 to 55% B, 10–13 min increase from 55 to 95% B, 13–15 min maintain 5% A and 95% B, 15–15.1 min decrease from 95 – 0% B, 15.1-18 min equilibration at 100% A. The column temperature was maintained at 40°C and sample volumes of 10 μL were injected. |
| Instrument Name: | Waters Xevo G2-XS UPLC/MS/MS |
| Column Name: | Waters ACQUITY UPLC HSS T3 (150 x 2.1mm,1.8um) |
| Column Temperature: | 40°C |
| Flow Gradient: | 0–1.5 min 0% B, 1.5–4 min increase from 0 to 20% B, 4–6 min maintain at 20% B, 6–10.5 min increase from 20 to 55% B, 10–13 min increase from 55 to 95% B, 13–15 min maintain at 95% B, 15–15.1 min decrease from 95 – 0% B, 15.1-18 min equilibration at 0% B |
| Flow Rate: | 300 μl/min |
| Solvent A: | 97% water/3% methanol; 10 mM tributylamine; 15 mM acetic acid (pH 5.0 ± 0.05) |
| Solvent B: | 100% methanol |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN007082 |
| Analysis Type: | MS |
| Chromatography ID: | CH005379 |
| Num Factors: | 4 |
| Num Metabolites: | 30 |
| Units: | peak area/mg of tissues |
