Summary of Study ST001964
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 PR001095. The data can be accessed directly via it's Project DOI: 10.21228/M85976 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST001964 |
| Study Title | Quantitative genome-scale analysis of human liver reveals dysregulation of glycosphingolipid pathways in progressive nonalcoholic fatty liver disease |
| Study Summary | Nonalcoholic fatty liver disease (NAFLD) is a well-defined chronic liver diseases closely related with metabolic disorders. The prevalence of NAFLD is rapidly increasing worldwide, while the pathology and the underlying mechanisms driving NAFLD are not fully understood. In NAFLD, a series of metabolic changes takes place in the liver. However, the alteration of the metabolic pathways in the human liver along the progression of NAFLD, i.e., the transition from nonalcoholic steatosis (NAFL) to steatohepatitis (NASH) through cirrhosis remains to be discovered. Here, we sought to examine the metabolic pathways of the human liver across the full histological spectrum of NAFLD. We analyzed the whole liver tissue transcriptomic (RNA-Seq) and serum metabolomics data obtained from a large, prospectively enrolled cohort of histologically characterized patients derived from the European NAFLD Registry (n=206), and developed genome-scale metabolic models (GEMs) of human hepatocytes at different stages of NAFLD. The integrative approach employed in this study has enabled us to understand the regulation of the metabolic pathways of human liver in NAFL, and with progressive NASH-associated fibrosis (F0–F4). Our study identified several metabolic signatures in the liver and blood of these patients, specifically highlighting the alteration of vitamins (A, E) and glycosphingolipids (GSLs), and their link with complex glycosaminoglycans (GAGs) in advanced fibrosis. The study provides insights into the underlying pathways of the progressive fibrosing steatohepatitis. Furthermore, by applying genome-scale metabolic modeling (GSMM), we were able to identify the metabolic differences among carriers of widely validated genetic variants associated with NAFLD / NASH disease severity in three genes (PNPLA3, TM6SF2 and HSD17B13). |
| Institute | University of Turku |
| Last Name | Sen |
| First Name | Partho |
| Address | Systems Medicine group, Turku Bioscience, University of Turku (UTU), Tykistökatu 6B, P.O. Box 123 FIN-20521 Turku, Finland |
| partho.sen@utu.fi | |
| Phone | Phone: +358 469608145 |
| Submit Date | 2021-02-18 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzML |
| Analysis Type Detail | GC-MS |
| Release Date | 2022-01-03 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN003202 |
|---|---|
| Analysis type | MS |
| Chromatography type | GC |
| Chromatography system | Agilent 7890B |
| Column | Zebron ZB-SemiVolatiles (20m x 0.18mm,0.18m) |
| MS Type | EI |
| MS instrument type | GC x GC-TOF |
| MS instrument name | Agilent 7200 QTOF |
| Ion Mode | UNSPECIFIED |
| Units | log2 autoscaled abundance |
