PXD058489

PXD058489 is an original dataset announced via ProteomeXchange.

Title	A disease of metabolism: Defining lipedema’s molecular hallmarks by multi-omics approach for disease prediction
Description	Characterized by pathologic subcutaneous adipose tissue development in the limbs, lipedema is a chronic disease in women. Molecular disease pathways and potential drug target genes remain to be found. In this study, we investigated the molecular and cellular hallmarks of lipedema using a multi-omics approach. We found adipokine dysregulation in early stage lipedema patients, which points towards the adipocyte as a key player. Unexpectedly, lipedema patients’ serum lactosyl- and hexosyl-sphingolipids increased compared to control subjects, when adjusted for age. Additionally, we observed immune cell exclusion from adipose tissue in lipedema patients. In subjects with lipedema, both expression of genes in VEGF signaling pathways (blood vessel/vascular development) as well as VEGF protein levels in serum increased. Expression of genes in the inflammatory response pathway points towards the absence of adipose tissue inflammation, and is in line with reduced serum inflammatory markers IL5 and FLT3L. The systemic reduction of serum glutamic acid levels, regulation of protein and RNA glutamic—pyruvic transaminase and reduced glutathione levels could link reduced inflammation with metabolic processes. The protein pathways for blood coagulation, and regulation of body fluid levels are most strongly down regulated. There is a case to be made that lipedema could be caused by dysregulation of metabolism that leads to immune cell exclusion. These findings provide new insights into the pathogenesis of lipedema and suggest potential targets for therapeutic intervention. Last but not least we used machine learning to train support vector machine based models with either serum sphingolipids and adipokines or adipose tissue RNA to predict the lipedema phenotype at a high accuracy.
HostingRepository	PRIDE
AnnounceDate	2025-03-17
AnnouncementXML	Submission_2025-03-17_10:36:57.067.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD058489
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Paul Langlais
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-02 13:25:07	ID requested
⏵ 1	2025-03-17 10:36:57	announced

10.6019/PXD058489;

submitter keyword: Menopause, adipose,lipedema

Leon Straub
contact affiliation	UT Southwestern
contact email	Leon.Straub@UTSouthwestern.edu
lab head
Paul Langlais
contact affiliation	University of Arizona
contact email	langlais@deptofmed.arizona.edu
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/2025/03/PXD058489

PRIDE project URI

• PRIDE
  1. PXD058489
     1. Label: PRIDE project
     2. Name: A disease of metabolism: Defining lipedema’s molecular hallmarks by multi-omics approach for disease prediction