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
Email	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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Sample Preparation:

Sampleprep ID:	SP003454
Sampleprep Summary:	Lipids from whole liver were extracted using a monophasic extraction protocol. Briefly, 5-10 mg of liver was homogenized using a Precellys tissue homogenizer in 100 µL 1:1 butanol-methanol, containing 5 µL of SPLASH® II LIPIDOMIX® Mass Spec Standard (part no. 330709W, Avanti Polar Lipids Inc) and 5 uL of Ceramide LIPIDOMIX® Mass Spec Standard (part no. 330712X, Avanti Polar Lipids Inc). Samples were mixed for 1 h at room temperature, centrifuged (14,000 g, 10 min, 20 ⁰C) and transferred into sample vials with glass inserts for analysis.

Sampleprep ID:

SP003454

Sampleprep Summary:

Lipids from whole liver were extracted using a monophasic extraction protocol. Briefly, 5-10 mg of liver was homogenized using a Precellys tissue homogenizer in 100 µL 1:1 butanol-methanol, containing 5 µL of SPLASH® II LIPIDOMIX® Mass Spec Standard (part no. 330709W, Avanti Polar Lipids Inc) and 5 uL of Ceramide LIPIDOMIX® Mass Spec Standard (part no. 330712X, Avanti Polar Lipids Inc). Samples were mixed for 1 h at room temperature, centrifuged (14,000 g, 10 min, 20 ⁰C) and transferred into sample vials with glass inserts for analysis.