PXD047957 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-12-19 10:22:31 | ID requested | |
⏵ 1 | 2024-06-12 00:20:37 | announced | |
Publication List
Keyword List
submitter keyword: pan-PPAR agonist, proteomics, lipid metabolism,Lysosomal acid lipase deficiency, liver inflammation, plasma lipoproteins, lanifibranor |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD047957
- Label: PRIDE project
- Name: Lanifibranor reduces inflammation and improves dyslipidemia in lysosomal acid lipase-deficient mice