Summary of project PR002403
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 PR002403. The data can be accessed directly via it's Project DOI: 10.21228/M81C2R This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002403 |
| Project DOI: | doi: 10.21228/M81C2R |
| Project Title: | Shift in the urinary metabolome associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin activation of the hepatic aryl hydrocarbon receptor |
| Project Summary: | Epidemiological evidence suggests an association between dioxin and dioxin-like compound (DLC) exposure and human liver disease. In rodents, 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. Although the effects of TCDD toxicity are mediated by aryl hydrocarbon receptor (AHR) activation, the underlying mechanisms of TCDD-induced liver toxicity are not well understood. In the present study, male C57BL/6NCrl mice were gavaged every 4 days for 28 days with 0.03 - 30 µg/kg TCDD or sesame oil vehicle and evaluated for liver histopathology and gene expression as well as complementary 1-dimensional proton magnetic resonance (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. Hepatic differential gene expression of rate-limiting enzymes of choline, gloxylate, and amino acid metabolism coincided with the altered urinary metabolites. Published single-nuclear RNA-seq (snRNA-seq), AHR ChIP-seq, and AHR knockout gene expression datasets provided further support for hepatic |
| Institute: | Michigan State University |
| Department: | Biochemistry and Molecular Biology |
| Last Name: | Sink |
| First Name: | Warren |
| Address: | 603 Wilson Rd, East Lansing, Michigan, 48824, USA |
| Email: | sinkwarr@msu.edu |
| Phone: | 6162953496 |
| Project Comments: | The urine samples were collected by the Zacharewski lab at Michigan State University. The samples were evaluated with 1-dimensional 1H NMR by Dr. Ali Yilmaz at Corewell Health Research Institute. The data upload was done by Warren Sink from the Zacharewski lab. |
Summary of all studies in project PR002403
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003845 | Shift in the urinary metabolome associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin activation of the hepatic aryl hydrocarbon receptor | Mus musculus | Michigan State University | NMR | 2025-04-07 | 1 | 40 | Uploaded data (40.4M)* |
