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PXD051606-1

PXD051606 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDeletion of the mitochondrial peptidase miPEP in adipose tissue protects against obesity and insulin resistance by increasing adaptive thermogenesis
DescriptionMitochondria 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.
HostingRepositoryPRIDE
AnnounceDate2024-08-11
AnnouncementXMLSubmission_2024-08-10_16:54:00.426.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterDavid James
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480; Q Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-04-20 11:52:59ID requested
12024-08-10 16:54:01announced
Publication List
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, รถ, 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]
Keyword List
submitter keyword: insulin resistance, miPEP, thermogenesis, adipose,mitochondria
Contact List
Professor David James
contact affiliationCharles Perkins Centre, School of Life and Environmental Sciences, University of Sydney, Sydney, Australia.
contact emaildavid.james@sydney.edu.au
lab head
David James
contact affiliationThe University of Sydney
contact emaildavid.james@sydney.edu.au
dataset submitter
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Dataset FTP location
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