Summary of project PR001560
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 PR001560. The data can be accessed directly via it's Project DOI: 10.21228/M8242N This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001560 |
| Project DOI: | doi: 10.21228/M8242N |
| Project Title: | Integrated gut microbiome and lipidomic analyses in animal models of Wilson disease reveal a role of intestine ATP7B in copper-related metabolic dysregulation |
| Project Summary: | Although the main pathogenic mechanism of Wilson disease (WD) is related to copper accumulation in the liver and brain, there is limited knowledge about the role of ATP7B copper transporter in extra-hepatic organs, including the intestine, and how it could affect metabolic manifestations of the disease. The aims of the present study were to profile and correlate the gut microbiota and lipidome in mouse models of WD, and to study the metabolic effects of intestine-specific ATP7B deficiency in a newly generated mouse model. Animal models of WD presented reduced gut microbiota diversity compared to mice with normal copper metabolism. Comparative prediction analysis of the functional metagenome showed the involvement of several pathways including amino acid, carbohydrate, and lipid metabolisms. Lipidomic profiles showed dysregulated tri- and diglyceride, phospholipid, and sphingolipid metabolism. When challenged with a high-fat diet, Atp7bΔIEC mice confirmed profound deregulation of fatty acid desaturation and sphingolipid metabolism pathways as well as altered APOB48 distribution in intestinal epithelial cells. Gut microbiome and lipidomic analyses reveal integrated metabolic changes underlying the systemic manifestations of WD. Intestine-specific ATP7B deficit affects both intestine and systemic response to high-fat challenge. WD is as systemic disease and organ-specific ATP7B variants can explain the varied phenotypic presentations. |
| Institute: | University of California, Davis |
| Department: | Department of Internal Medicine, Division of Hepatology/Gastroenterology |
| Last Name: | Sarode |
| First Name: | Gaurav Vilas |
| Address: | 451 E. Health Sciences Dr. Genome and Biomedical Sciences Facility Room 6404A Davis, CA 95616 |
| Email: | gsarode@ucdavis.edu |
| Phone: | 5307526715 |
| Funding Source: | National Institutes of Health grants R01DK104770 (V.M.) |
Summary of all studies in project PR001560
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002423 | Integrated gut microbiome and lipidomic analyses in animal models of Wilson disease reveal a role of intestine ATP7B in copper-related metabolic dysregulation (Part 1) | Mus musculus | University of California, Davis | MS* | 2023-06-20 | 1 | 210 | Uploaded data (40G)* |
| ST002424 | Integrated gut microbiome and lipidomic analyses in animal models of Wilson disease reveal a role of intestine ATP7B in copper-related metabolic dysregulation (Part 2) | Mus musculus | University of California, Davis | MS* | 2023-06-20 | 1 | 96 | Uploaded data (16G)* |
| ST002425 | Integrated gut microbiome and lipidomic analyses in animal models of Wilson disease reveal a role of intestine ATP7B in copper-related metabolic dysregulation (Part 3) | Mus musculus | University of California, Davis | MS* | 2023-06-20 | 1 | 30 | Uploaded data (2.3G)* |
