PXD072248-1

PXD072248 is an original dataset announced via ProteomeXchange.

Title	Functional annotation of insulin-responsive genes in human adipocytes reveals PLCXD1 as a lipid storage regulator
Description	Insulin regulates adipocyte biology partly by modulating gene expression, still many insulin-responsive targets remain uncharacterized. Here, we integrate three transcriptomic datasets to define insulin-regulated genes and assess their functions in human adipocytes using a multiparametric lipid turnover screen. Our results reveal four major clusters involved in metabolic regulation, transcription, stress responses, and lipid metabolism. Among lipid-related hits, phospholipase C X domain-containing protein-1 (PLCXD1) emerges as a regulator of insulin-stimulated lipogenesis, without affecting lipolysis or adipogenesis. PLCXD1 is transcriptionally induced by insulin via sterol regulatory element-binding proteins, an induction impaired in insulin resistance. This atypical phospholipase is genetically linked to increased fat mass, localizes to early endosomes and catalyzes phosphatidylinositol conversion into diacylglycerol, which appears necessary for lipid storage. Furthermore, we identify residues required for enzymatic activity without affecting localization. Proteomic assessment was performed in PLCXD1 depleted adipocytes to gain insight into PLCXD1 function and assess compensatory protein changes. Altogether, our results uncover PLCXD1 as an insulin-regulated enzyme coupling intracellular membrane signaling to lipid metabolism across physiological and pathological states.
HostingRepository	PRIDE
AnnounceDate	2026-06-02
AnnouncementXML	Submission_2026-06-02_06:21:55.802.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Natalie Krahmer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-20 18:18:11	ID requested
⏵ 1	2026-06-02 06:21:56	announced

Dataset with its publication pending

submitter keyword: phosphoinositide lipase, lipolysis,White adipose tissue, adipocyte, insulin action, lipogenesis, PLCXD1, lipid turnover

Natalie Krahmer
contact affiliation	Institute for Diabetes and Obesity, Helmholtz Zentrum München, Neuherberg, Germany. and German Center for Diabetes Research (DZD), Neuherberg, Germany;d German Center for Diabetes Research, Neuherberg, Germany
contact email	natalie.krahmer@helmholtz-munich.de
lab head
Natalie Krahmer
contact affiliation	Helmholtz Center Munich
contact email	natalie.krahmer@helmholtz-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD072248
     1. Label: PRIDE project
     2. Name: Functional annotation of insulin-responsive genes in human adipocytes reveals PLCXD1 as a lipid storage regulator