PXD063623-1

PXD063623 is an original dataset announced via ProteomeXchange.

Title	Deletion of matrix metalloproteinase-12 improves energy metabolism and brown adipose tissue function in mice prone to develop cardiometabolic disease
Description	Matrix metalloproteinase-12 (MMP12) is a proinflammatory protein secreted by macrophages. We have previously demonstrated that the genetic deletion of MMP12 in a cardiometabolic mouse model (low-density lipoprotein receptor-deficient (LdlrKO) mice fed a high-fat, sucrose- and cholesterol-enriched diet) ameliorated obesity-induced low-grade inflammation, white adipose tissue dysfunction, and atherosclerosis. Here, we hypothesized that the deletion of MMP12 might also positively affect whole-body energy metabolism and/or brown adipose tissue (BAT) function. Ldlr/Mmp12 double knockout (DKO) mice housed at room temperature (22°C) showed increased energy expenditure and decreased BAT size and triglyceride (TG) content. Untargeted proteomic analyses revealed the upregulation of several proteins and pathways related to mitochondrial function, glucose metabolism, and fatty acid oxidation in the BAT of DKO mice, whereas abundance of proteins and pathways associated with inflammation were reduced. In addition, DKO mice exhibited reduced macrophage infiltration in BAT with the infiltrating macrophages showing lower expression of lipid-associated marker genes. As we detected MMP12 expression in the mitochondrial fraction of BAT, its absence in DKO BAT was consistent with reduced oxygen consumption, compactness, and sphericity of the mitochondria. Following an acute cold exposure, DKO mice had decreased BAT weights and circulating lipid concentrations, especially very low-density lipoprotein-TG and LDL-cholesterol, and increased expression of thermogenic genes. We conclude that MMP12 may play a detrimental role in whole-body energy homeostasis and thermogenesis, as it triggers macrophage infiltration, inflammation, and mitochondria dysfunction in BAT.
HostingRepository	PRIDE
AnnounceDate	2026-01-19
AnnouncementXML	Submission_2026-01-18_16:36:33.338.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: NEWT:10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-05 16:06:51	ID requested
⏵ 1	2026-01-18 16:36:34	announced

Amor M, Diaz M, Fuerlinger A, Svecla M, Bianco V, Schooltink L, Dobrijevi, ć A, Schwarz B, Akhmetshina A, Vuji, ć N, Korbelius M, Hirtl M, Buerger M, Pirchheim A, Rainer S, Schauer S, Beretta G, Goessler W, Kolb D, Hoefler G, Hackl H, Madreiter-Sokolowski C, Abdellatif M, Norata GD, Kratky D, Deletion of MMP12 improves energy metabolism and brown adipose tissue function in mice prone to cardiometabolic disease. J Lipid Res, 67(1):100951(2026) [pubmed]

10.1016/j.jlr.2025.100951;

submitter keyword: Cold exposure, Untargeted proteomics,BAT, Mitochondrial processes, Ldlr-deficient mice, MMP12

Dagmar Kratky
contact affiliation	Professor of Biochemistry, Medical University of Graz, Austria
contact email	dagmar.kratky@medunigraz.at
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/2026/01/PXD063623

PRIDE project URI

• PRIDE
  1. PXD063623
     1. Label: PRIDE project
     2. Name: Deletion of matrix metalloproteinase-12 improves energy metabolism and brown adipose tissue function in mice prone to develop cardiometabolic disease