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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Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id	local_sample_id	Mouse Strain	Food source	Sample source
SA361345	210226_Hamze_MM-1835_055p	A/J	Chow	Liver
SA361346	210226_Hamze_MM-1835_051n	A/J	Chow	Liver
SA361347	210226_Hamze_MM-1835_053n	A/J	Chow	Liver
SA361348	210226_Hamze_MM-1835_055n	A/J	Chow	Liver
SA361349	210226_Hamze_MM-1835_057n	A/J	Chow	Liver
SA361350	210226_Hamze_MM-1835_059n	A/J	Chow	Liver
SA361351	210226_Hamze_MM-1835_061n	A/J	Chow	Liver
SA361352	210226_Hamze_MM-1835_063n	A/J	Chow	Liver
SA361353	210226_Hamze_MM-1835_065n	A/J	Chow	Liver
SA361354	210226_Hamze_MM-1835_067n	A/J	Chow	Liver
SA361355	210226_Hamze_MM-1835_068n	A/J	Chow	Liver
SA361356	210226_Hamze_MM-1835_053p	A/J	Chow	Liver
SA361357	210226_Hamze_MM-1835_051p	A/J	Chow	Liver
SA361358	210226_Hamze_MM-1835_068p	A/J	Chow	Liver
SA361359	210226_Hamze_MM-1835_067p	A/J	Chow	Liver
SA361360	210226_Hamze_MM-1835_059p	A/J	Chow	Liver
SA361361	210226_Hamze_MM-1835_061p	A/J	Chow	Liver
SA361362	210226_Hamze_MM-1835_065p	A/J	Chow	Liver
SA361363	210226_Hamze_MM-1835_057p	A/J	Chow	Liver
SA361364	210226_Hamze_MM-1835_063p	A/J	Chow	Liver
SA361365	210226_Hamze_MM-1835_056p	A/J	NASH	Liver
SA361366	210226_Hamze_MM-1835_064p	A/J	NASH	Liver
SA361367	210226_Hamze_MM-1835_052n	A/J	NASH	Liver
SA361368	210226_Hamze_MM-1835_054n	A/J	NASH	Liver
SA361369	210226_Hamze_MM-1835_066p	A/J	NASH	Liver
SA361370	210226_Hamze_MM-1835_056n	A/J	NASH	Liver
SA361371	210226_Hamze_MM-1835_058n	A/J	NASH	Liver
SA361372	210226_Hamze_MM-1835_062n	A/J	NASH	Liver
SA361373	210226_Hamze_MM-1835_060n	A/J	NASH	Liver
SA361374	210226_Hamze_MM-1835_062p	A/J	NASH	Liver
SA361375	210226_Hamze_MM-1835_064n	A/J	NASH	Liver
SA361376	210226_Hamze_MM-1835_066n	A/J	NASH	Liver
SA361377	210226_Hamze_MM-1835_060p	A/J	NASH	Liver
SA361378	210226_Hamze_MM-1835_052p	A/J	NASH	Liver
SA361379	210226_Hamze_MM-1835_058p	A/J	NASH	Liver
SA361380	210226_Hamze_MM-1835_054p	A/J	NASH	Liver
SA361381	210226_Hamze_MM-1835_030p	BALBc	Chow	Liver
SA361382	210226_Hamze_MM-1835_029p	BALBc	Chow	Liver
SA361383	210226_Hamze_MM-1835_034p	BALBc	Chow	Liver
SA361384	210226_Hamze_MM-1835_033p	BALBc	Chow	Liver
SA361385	210226_Hamze_MM-1835_037p	BALBc	Chow	Liver
SA361386	210226_Hamze_MM-1835_029n	BALBc	Chow	Liver
SA361387	210226_Hamze_MM-1835_030n	BALBc	Chow	Liver
SA361388	210226_Hamze_MM-1835_033n	BALBc	Chow	Liver
SA361389	210226_Hamze_MM-1835_034n	BALBc	Chow	Liver
SA361390	210226_Hamze_MM-1835_035n	BALBc	Chow	Liver
SA361391	210226_Hamze_MM-1835_036n	BALBc	Chow	Liver
SA361392	210226_Hamze_MM-1835_037n	BALBc	Chow	Liver
SA361393	210226_Hamze_MM-1835_036p	BALBc	Chow	Liver
SA361394	210226_Hamze_MM-1835_035p	BALBc	Chow	Liver
SA361395	210226_Hamze_MM-1835_026n	BALBc	NASH	Liver
SA361396	210226_Hamze_MM-1835_024n	BALBc	NASH	Liver
SA361397	210226_Hamze_MM-1835_023n	BALBc	NASH	Liver
SA361398	210226_Hamze_MM-1835_022n	BALBc	NASH	Liver
SA361399	210226_Hamze_MM-1835_021n	BALBc	NASH	Liver
SA361400	210226_Hamze_MM-1835_022p	BALBc	NASH	Liver
SA361401	210226_Hamze_MM-1835_021p	BALBc	NASH	Liver
SA361402	210226_Hamze_MM-1835_025n	BALBc	NASH	Liver
SA361403	210226_Hamze_MM-1835_028n	BALBc	NASH	Liver
SA361404	210226_Hamze_MM-1835_027n	BALBc	NASH	Liver
SA361405	210226_Hamze_MM-1835_023p	BALBc	NASH	Liver
SA361406	210226_Hamze_MM-1835_024p	BALBc	NASH	Liver
SA361407	210226_Hamze_MM-1835_025p	BALBc	NASH	Liver
SA361408	210226_Hamze_MM-1835_026p	BALBc	NASH	Liver
SA361409	210226_Hamze_MM-1835_027p	BALBc	NASH	Liver
SA361410	210226_Hamze_MM-1835_028p	BALBc	NASH	Liver
SA361411	210226_Hamze_MM-1835_006p	BL6	Chow	Liver
SA361412	210226_Hamze_MM-1835_003p	BL6	Chow	Liver
SA361413	210226_Hamze_MM-1835_004p	BL6	Chow	Liver
SA361414	210226_Hamze_MM-1835_005p	BL6	Chow	Liver
SA361415	210226_Hamze_MM-1835_010p	BL6	Chow	Liver
SA361416	210226_Hamze_MM-1835_007p	BL6	Chow	Liver
SA361417	210226_Hamze_MM-1835_008p	BL6	Chow	Liver
SA361418	210226_Hamze_MM-1835_009p	BL6	Chow	Liver
SA361419	210226_Hamze_MM-1835_002n	BL6	Chow	Liver
SA361420	210226_Hamze_MM-1835_002p	BL6	Chow	Liver
SA361421	210226_Hamze_MM-1835_001n	BL6	Chow	Liver
SA361422	210226_Hamze_MM-1835_001p	BL6	Chow	Liver
SA361423	210226_Hamze_MM-1835_007n	BL6	Chow	Liver
SA361424	210226_Hamze_MM-1835_009n	BL6	Chow	Liver
SA361425	210226_Hamze_MM-1835_008n	BL6	Chow	Liver
SA361426	210226_Hamze_MM-1835_010n	BL6	Chow	Liver
SA361427	210226_Hamze_MM-1835_006n	BL6	Chow	Liver
SA361428	210226_Hamze_MM-1835_005n	BL6	Chow	Liver
SA361429	210226_Hamze_MM-1835_004n	BL6	Chow	Liver
SA361430	210226_Hamze_MM-1835_003n	BL6	Chow	Liver
SA361431	210226_Hamze_MM-1835_011p	BL6	NASH	Liver
SA361432	210226_Hamze_MM-1835_013p	BL6	NASH	Liver
SA361433	210226_Hamze_MM-1835_014p	BL6	NASH	Liver
SA361434	210226_Hamze_MM-1835_015p	BL6	NASH	Liver
SA361435	210226_Hamze_MM-1835_016p	BL6	NASH	Liver
SA361436	210226_Hamze_MM-1835_017p	BL6	NASH	Liver
SA361437	210226_Hamze_MM-1835_018p	BL6	NASH	Liver
SA361438	210226_Hamze_MM-1835_019p	BL6	NASH	Liver
SA361439	210226_Hamze_MM-1835_020p	BL6	NASH	Liver
SA361440	210226_Hamze_MM-1835_012p	BL6	NASH	Liver
SA361441	210226_Hamze_MM-1835_020n	BL6	NASH	Liver
SA361442	210226_Hamze_MM-1835_011n	BL6	NASH	Liver
SA361443	210226_Hamze_MM-1835_012n	BL6	NASH	Liver
SA361444	210226_Hamze_MM-1835_013n	BL6	NASH	Liver