PXD042478

PXD042478 is an original dataset announced via ProteomeXchange.

Title	Pronounced metabolic alterations and susceptibility to inflammation, fibrosis, and cancer in livers from lysosomal acid lipase-deficient mice
Description	Lysosomal acid lipase (LAL) is the sole lysosomal enzyme responsible for the degradation of cholesteryl esters and triacylglycerols at acidic pH. Impaired LAL activity leads to LAL deficiency (LAL-D), a severe and fatal disease characterized by ectopic lysosomal lipid accumulation. Reduced LAL activity also contributes to the development and progression of non-alcoholic fatty liver disease (NAFLD). To advance our understanding of LAL-related liver pathologies, we performed comprehensive proteomic profiling of livers from mice with systemic genetic loss of LAL (Lal-/-) and from mice with hepatocyte-specific LAL-D (hepLal-/-). Lal-/- mice exhibited drastic proteome alterations, including dysregulation of multiple proteins related to metabolism, inflammation, liver fibrosis, and cancer. Global loss of LAL activity impaired both acidic and neutral lipase activities and resulted in hepatic lipid accumulation, indicating a complete metabolic shift in Lal-/- livers. Hepatic inflammation and immune cell infiltration were evident, with numerous upregulated inflammation-related gene ontology biological process terms. In contrast, both young and mature hepLal-/- mice displayed only minor changes in the liver proteome, suggesting that loss of LAL solely in hepatocytes does not phenocopy metabolic alterations observed in mice globally lacking LAL. These findings provide valuable insights into the mechanisms underlying liver dysfunction in LAL-D and may help in understanding why decreased LAL activity contributes to NAFLD. Our study highlights the importance of LAL in maintaining liver homeostasis and demonstrates the drastic consequences of its global deficiency on the liver proteome and liver function.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:11:33.546.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Laura Liesinger
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-24 09:59:26	ID requested
1	2023-10-24 13:07:51	announced
⏵ 2	2023-11-14 09:11:43	announced	2023-11-14: Updated project metadata.

Bradi, ć I, Liesinger L, Kuentzel KB, Vuji, ć N, Trauner M, Birner-Gruenberger R, Kratky D, Metabolic changes and propensity for inflammation, fibrosis, and cancer in livers of mice lacking lysosomal acid lipase. J Lipid Res, 64(9):100427(2023) [pubmed]

submitter keyword: Lysosomal acid lipase (LAL), LAL deficiency, liver, mouse, non-alcoholic fatty liver disease (NAFLD)

Ruth Birner-Gruenberger
contact affiliation	Faculty of Technical Chemistry, Institute of Chemical Technologies and Analytics, Technische Universität Wien (TU Wien), 1060 Vienna, Austria; Diagnostic and Research Institute of Pathology, Medical University of Graz, 8036 Graz, Austria; BiotechMed-Graz, Omics Center Graz, 8010 Graz, Austria;
contact email	ruth.birner-gruenberger@tuwien.ac.at
lab head
Laura Liesinger
contact affiliation	Faculty of Technical Chemistry, Institute of Chemical Technologies and Analytics, Technische Universität Wien (TU Wien), 1060 Vienna, Austria;
contact email	laura.liesinger@tuwien.ac.at
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042478
     1. Label: PRIDE project
     2. Name: Pronounced metabolic alterations and susceptibility to inflammation, fibrosis, and cancer in livers from lysosomal acid lipase-deficient mice