PXD051606-1

PXD051606 is an original dataset announced via ProteomeXchange.

Title	Deletion of the mitochondrial peptidase miPEP in adipose tissue protects against obesity and insulin resistance by increasing adaptive thermogenesis
Description	Mitochondria are pivotal for cellular metabolism, serving as sources and targets of nutrient intermediates from converging metabolic pathways. Here, we demonstrate that insulin resistance leads to a marked alteration in the mitochondrial proteome of adipocytes. Analysis across multiple insulin resistance models revealed a consistent decrease in the level of the mitochondrial processing peptidase miPEP, suggesting a potential role for miPEP in the aetiology of insulin resistance. Adipocyte specific miPEP knockout mice demonstrated a strong phenotype marked by a browning-independent increment in energy expenditure, enhanced insulin sensitivity, and reduced adiposity, despite normal food intake and physical activity. These phenotypes vanished when mice were housed at thermoneutrality suggesting that miPEP deletion triggers a compensatory enhancement in thermogenesis protecting against metabolic dysfunction. Tissue specific analysis of miPEP deficient mice revealed a selective increment in muscle metabolism evidenced by increased basal and insulin induced glucose uptake and upregulation of the protein Fbp2, involved in energy wasting via futile cycling. These findings suggest that miPEP deletion initiates a compensatory increase in thermogenesis, acting as a protective mechanism against diet-induced insulin resistance.
HostingRepository	PRIDE
AnnounceDate	2024-08-11
AnnouncementXML	Submission_2024-08-10_16:54:00.426.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David James
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480; Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-20 11:52:59	ID requested
⏵ 1	2024-08-10 16:54:01	announced

10.1016/j.molmet.2024.101983;

Diaz-Vegas A, Cooke KC, Cutler HB, Yau B, Masson SWC, Harney D, Fuller OK, Potter M, Madsen S, Craw NR, Zhang Y, Moreno CL, Kebede MA, Neely GG, St, ö, ckli J, Burchfield JG, James DE, Deletion of miPEP in adipocytes protects against obesity and insulin resistance by boosting muscle metabolism. Mol Metab, 86():101983(2024) [pubmed]

submitter keyword: insulin resistance, miPEP, thermogenesis, adipose,mitochondria

Professor David James
contact affiliation	Charles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia.
contact email	david.james@sydney.edu.au
lab head
David James
contact affiliation	The University of Sydney
contact email	david.james@sydney.edu.au
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/2024/08/PXD051606

PRIDE project URI

• PRIDE
  1. PXD051606
     1. Label: PRIDE project
     2. Name: Deletion of the mitochondrial peptidase miPEP in adipose tissue protects against obesity and insulin resistance by increasing adaptive thermogenesis