PXD047957

PXD047957 is an original dataset announced via ProteomeXchange.

Title	Lanifibranor reduces inflammation and improves dyslipidemia in lysosomal acid lipase-deficient mice
Description	Background & Aims Recent studies showed that patients suffering from lysosomal acid lipase-deficiency (LAL-D) benefit tremendously from enzyme replacement therapy (ERT), however, the outcomes on liver histology in treated patients were inconsistent. The promising results of the pan-PPAR agonist lanifibranor in alleviating liver inflammation in patients with nonalcoholic steatohepatitis prompted us to investigate the effects of lanifibranor on liver pathology in LAL knockout (Lal-/-) mice. Methods Lal-/- mice were daily gavaged with lanifibranor or vehicle for 21 days. The effects of the treatment were assessed by measuring body and organ weights, plasma lipids and lipoproteins, as well as hematological parameters, followed by liver proteomics and metabolomics. Results Lanifibranor treatment slightly altered organ weights without affecting the total body weight of Lal-/- mice. We observed major changes in the proteome, with multiple proteins related to lipid metabolism, peroxisomal, and mitochondrial activities being upregulated and inflammation-related proteins being downregulated in the livers of treated mice. Hepatic lipid levels and histology remained unaltered, whereas plasma triglyceride and total cholesterol levels were decreased and the lipoprotein profile of lanifibranor-treated Lal-/- mice improved. Conclusions Lanifibranor treatment positively affected liver inflammation and lipoprotein homeostasis in Lal-/- mice. These findings support further evaluation of lanifibranor in combination with ERT for phenotype improvement in Lal-/- mice and a possible exploration avenue for the treatment of LAL-D in humans.
HostingRepository	PRIDE
AnnounceDate	2024-06-12
AnnouncementXML	Submission_2024-06-12_00:20:37.527.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	2023-12-19 10:22:31	ID requested
⏵ 1	2024-06-12 00:20:37	announced

10.1016/J.GASTHA.2024.05.006;

submitter keyword: pan-PPAR agonist, proteomics, lipid metabolism,Lysosomal acid lipase deficiency, liver inflammation, plasma lipoproteins, lanifibranor

Atul Shahaji Deshmukh
contact affiliation	Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
contact email	atul.deshmukh@sund.ku.dk
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. PXD047957
     1. Label: PRIDE project
     2. Name: Lanifibranor reduces inflammation and improves dyslipidemia in lysosomal acid lipase-deficient mice