Summary of Study ST003326
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 PR002068. The data can be accessed directly via it's Project DOI: 10.21228/M89F9K This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003326 |
| Study Title | Lipidome profiling in non-alcoholic steatohepatitis identifies phosphatidylserine synthase 1 as a regulator of hepatic lipoprotein metabolism |
| Study Summary | Non-alcoholic fatty liver disease and more progressive non-alcoholic steatohepatitis (NASH) are characterized by defective lipid metabolism, which causes hepatic steatosis and disease progression. However, the changes in lipid metabolism in NASH are incompletely understood. Using lipidome profiling in livers of eight mouse strains, that differ substantially in susceptibility to NASH and liver fibrosis, as well as in patients with NASH, we show that phosphatidylserine (PS) accumulation and preservation of PS synthase 1 (PSS1) expression is associated with resistance to NASH. Mechanistically, PSS1 overexpression in the liver reduces hepatic steatosis through remodeling of the hepatic and liver-derived VLDL lipidome in mice with NASH. Specifically, we show an increase in VLDL ceramide content that suppresses the expression and activity of lipoprotein lipase (LPL) in skeletal muscle, thereby reducing VLDL-triglyceride clearance, fatty acid uptake and lipid accumulation in skeletal muscle. In addition, remodelling of lipoprotein composition inhibits the LDL receptor in the liver, likely contributing to the reduction in hepatic steatosis. Together, this study provides a unique resource describing lipidome changes in NASH, and identifies PSS1 as a novel regulator of hepatic lipoprotein metabolism. |
| Institute | University of Melbourne |
| Last Name | Montgomery |
| First Name | Magdalene |
| Address | Corner Grattan Street & Royal Parade |
| magdalene.montgomery@unimelb.edu.au | |
| Phone | 0422059907 |
| Submit Date | 2024-05-13 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | abf |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-10-21 |
| Release Version | 1 |
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Project:
| Project ID: | PR002068 |
| Project DOI: | doi: 10.21228/M89F9K |
| Project Title: | Lipidome profiling in non-alcoholic steatohepatitis identifies phosphatidylserine synthase 1 as a regulator of hepatic lipoprotein metabolism |
| Project Summary: | This project aimed to investigate the regulation of the hepatic lipidome in mice with non-alcoholic steatohepatitis (NASH) and liver fibrosis, and assess the differences in the hepatic lipidome in mouse strains susceptible or resistant to NASH and metabolic comorbidities. For this purpose, eight mouse strains were fed either a chow control diet or a western-style diet enriched in lipid, carbohydrate and cholesterol for 30-32 weeks, followed by in-depth metabolic phenotyping, assessment of liver pathology and the hepatic lipidome by LC/MS. This study found that resistance to diet-induced NASH in BALB/c mice was associated with increased hepatic phosphatidylserine (PS) content. Subsequent studies focusing on overexpression of PS synthase 1 (PSS1) in the livers of mice with steatosis or NASH show that increasing hepatic PS is associated with improvements in steatosis and/or inflammation. |
| Institute: | University of Melbourne |
| Last Name: | Montgomery |
| First Name: | Magdalene |
| Address: | Corner Grattan Street Royal Parade, Melbourne, Victoria, 3010, Australia |
| Email: | magdalene.montgomery@unimelb.edu.au |
| Phone: | 0422059907 |
