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.

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Study IDST001964
Study TitleQuantitative genome-scale analysis of human liver reveals dysregulation of glycosphingolipid pathways in progressive nonalcoholic fatty liver disease
Study SummaryNonalcoholic 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 NameSen
First NamePartho
AddressSystems Medicine group, Turku Bioscience, University of Turku (UTU), Tykistökatu 6B, P.O. Box 123 FIN-20521 Turku, Finland
Emailpartho.sen@utu.fi
PhonePhone: +358 469608145
Submit Date2021-02-18
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailGC-MS
Release Date2022-01-03
Release Version1
Partho Sen Partho Sen
https://dx.doi.org/10.21228/M85976
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id NAFLD.Status
SA1848351022385877NAFL
SA1848361022386427NAFL
SA1848371022386463NAFL
SA1848381022385860NAFL
SA1848391022386190NAFL
SA1848401022386958NAFL
SA1848411022386202NAFL
SA1848421022385788NAFL
SA1848431022385839NAFL
SA1848441022385926NASH_F0/1
SA1848451022386429NASH_F0/1
SA1848461022386914NASH_F0/1
SA1848471022386933NASH_F2
SA1848481022386978NASH_F2
SA1848491022386912NASH_F2
SA1848501022386446NASH_F2
SA1848511022386907NASH_F2
SA1848521022386453NASH_F2
SA1848531022386485NASH_F2
SA1848541022386214NASH_F2
SA1848551022385934NASH_F2
SA1848561022385844NASH_F2
SA1848571022385893NASH_F2
SA1848581022386136NASH_F2
SA1848591022384032NASH_F2
SA1848601022386192NASH_F2
SA1848611022386960NASH_F3
SA1848621022386981NASH_F3
SA1848631022385756NASH_F3
SA1848641022385774NASH_F3
SA1848651022385911NASH_F3
SA1848661022386508NASH_F3
SA1848671022385928NASH_F3
SA1848681022386159NASH_F3
SA1848691022386364NASH_F3
SA1848701022386899NASH_F3
SA1848711022385916NASH_F3
SA1848721022385855NASH_F4 / cirrhosis
SA1848731022387276NASH_F4 / cirrhosis
SA1848741022387147NASH_F4 / cirrhosis
SA1848751022386957NASH_F4 / cirrhosis
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