PXD056343-1

PXD056343 is an original dataset announced via ProteomeXchange.

Title	From LAL-D to MASLD: Insights into the role of LAL and Kupffer cells in liver inflammation and lipid metabolism
Description	Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent liver pathology worldwide, closely associated with obesity and metabolic disorders. Increasing evidence suggests that macrophages play a crucial role in the development of MASLD. Several human studies have shown an inverse correlation between circulating lysosomal acid lipase (LAL) activity and MASLD. LAL is the sole enzyme known to degrade cholesteryl esters (CE) and triacylglycerols in lysosomes. Consequently, these substrates accumulate when their enzymatic degradation is impaired due to LAL deficiency (LAL-D). This study aimed to investigate the role of hepatic LAL activity and liver-resident macrophages (i.e., Kupffer cells (KC)) in MASLD. To this end, we analyzed lipid metabolism in hepatocyte-specific (hep)Lal-/- mice and depleted KC with clodronate treatment. When fed a high-fat/high-cholesterol diet (HF/HCD), hepLal-/- mice exhibited CE accumulation and an increased number of macrophages in the liver without significantly affecting liver injury. KC were depleted upon clodronate administration, whereas infiltrating/proliferating CD68-expressing macrophages were less affected. This led to exacerbated hepatic CE accumulation and dyslipidemia, as evidenced by increased LDL-cholesterol concentrations. The results suggest that hepatic LAL-D in HF/HCD-fed mice leads to macrophage infiltration into the liver, and KC depletion further aggravates hepatic CE levels and dyslipidemia, a finding also supported by our proteomics analysis.
HostingRepository	PRIDE
AnnounceDate	2024-12-01
AnnouncementXML	Submission_2024-12-01_04:35:21.916.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ivan Bradić
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2024-09-28 02:42:52	ID requested
⏵ 1	2024-12-01 04:35:22	announced

Bradi, ć I, Kuentzel KB, Pirchheim A, Rainer S, Schwarz B, Trauner M, Larsen MR, Vuji, ć N, Kratky D, From LAL-D to MASLD: Insights into the role of LAL and Kupffer cells in liver inflammation and lipid metabolism. Biochim Biophys Acta Mol Cell Biol Lipids, 1870(1):159575(2025) [pubmed]

10.1016/j.bbalip.2024.159575;

submitter keyword: mouse, timsTOF Pro 2

Dagmar Kratky
contact affiliation	Molecular Biology and Biochemistry, Medical University of Graz
contact email	dagmar.kratky@medunigraz.at
lab head
Ivan Bradić
contact affiliation	Medical University of Graz
contact email	ibradic95@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD056343
     1. Label: PRIDE project
     2. Name: From LAL-D to MASLD: Insights into the role of LAL and Kupffer cells in liver inflammation and lipid metabolism