PXD048378-2

PXD048378 is an original dataset announced via ProteomeXchange.

Title	Regional differences in the small intestinal proteome of control mice and of mice lacking lysosomal acid lipase
Description	Background: Despite recent studies investigating the involvement of single cells in regional differences of the small intestine (SI), the metabolic contribution of the duodenum, jejunum, and ileum to the overall intestinal metabolism is still unclear. Basic procedures and main findings: Using an untargeted proteomics approach, we identified similarities and differences between the three intestinal tracts of C57BL/6J mice and found that proteins highly abundant in the mouse ileum correlated with high ileal expression of the corresponding genes in humans. Consistent with human data, we detected increasing abundance of lysosomal acid lipase (LAL) in C57BL/6J mice from the duodenum to ileum. LAL is the only enzyme known to degrade triacylglycerols and cholesteryl esters within the lysosome. Lipid accumulation in various organs along with gastrointestinal disturbances and malabsorption are typical features of patients and mice with LAL deficiency. We previously demonstrated that macrophages massively infiltrate the SI of Lal-deficient (KO) mice, especially the duodenum. To identify potential mechanisms behind the intestinal lipid accumulation and infiltration of immune cells, we used untargeted proteomics. Our results revealed a general inflammatory response and a common lipid-associated macrophage phenotype in all three intestinal segments of Lal KO mice, accompanied by higher expression of GPNMB and increased concentrations of circulating sTREM2. However, only duodenal macrophages activated a metabolic switch from lipids to other pathways such as glycolysis, TCA cycle, and oxidative phosphorylation to meet their high energy demand. Unexpectedly, these pathways were downregulated in the jejunum and ileum of Lal KO mice. Conclusion: Our results provide new insights into the process of absorption in control mice and the basis for novel markers of LAL-D and/or systemic inflammation in LAL-D.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:31:22.718.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Monika Svecla
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-10 02:10:48	ID requested
1	2024-02-20 06:53:39	announced
⏵ 2	2024-10-22 06:31:23	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: metabolism, proteomics,LAL, small intestine, macrophages

Giuseppe Danilo Norata
contact affiliation	Professor of Pharmacology Head Laboratory of Pharmacology of CardioImmunoMetabolic Disorders. Department of Pharmacological and Biomolecular Sciences “Rodolfo Paoletti", Coordinator Doctorate School of Pharmacological and Biomolecular Sciences, Experimental and Clinical, University of Milan, Italy.
contact email	danilo.norata@unimi.it
lab head
Monika Svecla
contact affiliation	University of Milan
contact email	monika.svecla@unimi.it
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048378

PRIDE project URI

• PRIDE
  1. PXD048378
     1. Label: PRIDE project
     2. Name: Regional differences in the small intestinal proteome of control mice and of mice lacking lysosomal acid lipase