PXD046703

PXD046703 is an original dataset announced via ProteomeXchange.

Title	The pseudokinase TRIB3 controls adipocyte lipid homeostasis and proliferation in vitro and in vivo
Description	Objective: In vivo studies in humans and mice have implicated the pseudokinase Tribbles 3 (TRIB3) in various aspects of energy metabolism. Whilst cell-based studies indicate a role for TRIB3 in adipocyte differentiation and function, it is unclear if and how these cellular functions may contribute to overall metabolic health. Methods: We investigated the metabolic phenotype of whole-body Trib3 knockout (Trib3KO) mice, focusing on adipocyte and adipose tissue functions. In addition, we combined lipidomics, transcriptomics, interactomics and phosphoproteomics analyses to elucidate cell-intrinsic functions of TRIB3 in pre- and mature adipocytes. Results: Trib3KO mice display increased adiposity, but their insulin sensitivity remains unaltered. Trib3KO adipocytes are smaller and display higher Proliferating Cell Nuclear Antigen (PCNA) levels, indicating potential alterations in either i) proliferation-differentiation balance, ii) impaired expansion after cell division, or iii) an altered balance between lipid storage and release, or a combination thereof. Lipidome analyses suggest TRIB3 involvement in the latter two processes, as triglyceride storage is reduced and membrane composition, which can restrain cellular expansion, is altered. Integrated interactome, phosphoproteome and transcriptome analyses support a role for TRIB3 in all three cellular processes through multiple cellular pathways, including Mitogen Activated Protein Kinase- (MAPK/ERK), Protein Kinase A (PKA)-mediated signaling and Transcription Factor 7 like 2 (TCF7L2) and Beta Catenin-mediated gene expression. Conclusions: Our !ndings support TRIB3 playing multiple distinct regulatory roles in the cytoplasm, nucleus and mitochondria, ultimately controlling adipose tissue homeostasis, rather than affecting a single cellular pathway.
HostingRepository	PRIDE
AnnounceDate	2026-01-26
AnnouncementXML	Submission_2026-01-26_08:06:44.477.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Harmjan Vos
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-06 07:58:39	ID requested
⏵ 1	2026-01-26 08:06:45	announced

10.1016/j.molmet.2023.101829;

Hern, á, ndez-Quiles M, Martinez Campesino L, Morris I, Ilyas Z, Reynolds S, Soon Tan N, Sobrevals Alcaraz P, Stigter ECA, Varga Á, Varga J, van Es R, Vos H, Wilson HL, Kiss-Toth E, Kalkhoven E, vivo. Mol Metab, 78():101829(2023) [pubmed]

submitter keyword: Tribbles

Adipocyte

Omics analyses

Metabolism

Eric Kalkhoven
contact affiliation	Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, 3C584 CG Utrecht, The Netherlands
contact email	e.kalkhoven@umcutrecht.nl
lab head
Harmjan Vos
contact affiliation	University Medical Center Utrecht Dept. Molecular Cancer Research
contact email	h.r.vos-3@umcutrecht.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046703
     1. Label: PRIDE project
     2. Name: The pseudokinase TRIB3 controls adipocyte lipid homeostasis and proliferation in vitro and in vivo