Summary of project PR002135
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 PR002135. The data can be accessed directly via it's Project DOI: 10.21228/M8NG0M This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002135 |
| Project DOI: | doi: 10.21228/M8NG0M |
| Project Title: | Gas chromatography - mass spectrometry (GC-MS) of liver hepatic extracts from adult male C57BL/6NCrl mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin |
| Project Summary: | Epidemiological evidence suggests an association between dioxin and dioxin-like compound (DLC) exposure and human liver disease. The prototypical DLC, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has been shown to induce the progression of reversible hepatic steatosis to steatohepatitis with periportal fibrosis and biliary hyperplasia in C57BL/6NCrl mice. Although the effects of TCDD toxicity are mediated by aryl hydrocarbon receptor (AHR) activation, the underlying mechanisms of TCDD-induced hepatotoxicity are unresolved. In the present study, male C57BL/6NCrl mice were gavaged every 4 days for 28 days with 0.03 - 30 µg/kg TCDD and evaluated for liver histopathology and gene expression as well as complementary 1-dimensional (1-D) 1H NMR urinary metabolic profiling. Urinary trimethylamine (TMA), trimethylamine N-oxide (TMAO), and 1-methylnicotinamide (1MN) levels were altered by TCDD at doses ≤ 3 µg/kg; other urinary metabolites, like glycolate, urocanate, and 3-hydroxyisovalerate, were only altered at doses that induced moderate to severe steatohepatitis. Bulk liver RNA-seq data suggested altered urinary metabolites correlated with hepatic differential gene expression corresponding to specific metabolic pathways. In addition to evaluating whether altered urinary metabolites were liver-dependent, published single-nuclear RNA-seq (snRNA-seq), AHR ChIP-seq, and AHR knockout gene expression datasets provided further support of hepatic cell-type and AHR-regulated dependency, respectively. Overall, TCDD-induced liver effects were preceded by and occurred with changes in urinary metabolite levels due to AHR-mediated changes in hepatic gene expression. |
| Institute: | Michigan State University |
| Department: | Biochemistry and Molecular Biology |
| Laboratory: | Dr. Tim Zacharewski's |
| Last Name: | Sink |
| First Name: | Warren |
| Address: | 603 Wilson Rd Rm 212, East Lansing, MI 48823 |
| Email: | sinkwarr@msu.edu |
| Phone: | 6162953496 |
Summary of all studies in project PR002135
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003476 | Gas chromatography - mass spectrometry (GC-MS) of liver hepatic extracts from adult male C57BL/6NCrl mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin | Mus musculus | Michigan State University | MS | 2024-11-01 | 1 | 50 | Uploaded data (667.1M)* |
