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PXD008660

PXD008660 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteome-wide diet-independent adipose tissue alterations link dendritic cells to 2-aminoadipoate associated insulin sensitivity.
DescriptionAdipose tissue dysfunction in obese humans is associated with disrupted metabolic homeostasis, insulin resistance, and type 2 diabetes mellitus (T2DM). In a mouse model that has preserved insulin sensitivity despite increased adiposity, we used unbiased three-dimensional integration of proteome profiles, metabolic profiles, and gene regulatory networks to understand adipose tissue proteome-wide changes and their metabolic implications. Multiple-dimensional liquid chromatography tandem mass spectrometry and extended multiplexing TMT labeling (24 biological samples) was used to analyze proteomes of epididymal adipose tissues isolated from wildtype (Csf2+/+) and GM-CSF driven dendritic cell deficient (Csf2-/-) mice that were fed low fat, high fat, or high fat plus cholesterol diets for 8 weeks. The peripheral metabolic health (as measured by body weight, adiposity, plasma fasting glucose, insulin, triglycerides, phospholipids, total cholesterol levels, and glucose and insulin tolerance tests) deteriorated with diet for both genotypes, while mice lacking Csf2 were protected from insulin resistance. Regardless of diet, 30, mostly mitochondrial metabolism proteins participating in amino acid and branched chain amino acid pathways were altered, between Csf2-/- and Csf2+/+ mice. Tissue DHTKD1 levels were >4-fold upregulated and plasma 2-aminoadipoate (2-AA) levels were >2 fold reduced in Csf2-/- mice. GM-CSF driven dendritic cells play a detrimental role in insulin sensitivity via lysine metabolism involving Dhtkd1/2-AA axis.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:08:14.948.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterPhillip Wilmarth
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion ETD
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-01-12 03:09:00ID requested
12018-08-06 07:38:17announced
22024-10-22 04:08:18announced2024-10-22: Updated project metadata.
Publication List
10.1038/s41598-018-29250-8;
Plubell DL, Fenton AM, Wilmarth PA, Bergstrom P, Zhao Y, Minnier J, Heinecke JW, Yang X, Pamir N, GM-CSF driven myeloid cells in adipose tissue link weight gain and insulin resistance via formation of 2-aminoadipate. Sci Rep, 8(1):11485(2018) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: insulin resistance, isobaric labeling, adipose tissue biology, inflammation, extended multiplexing, branched chain amino acid metabolism, quantitative proteomics,obesity
Contact List
Nathalie Pamir
contact affiliationKnight Cardiovascular Institute Oregon Health & Science University 3181 SW Sam Jackson Park Road Portland, Oregon 97239, USA
contact emailpamir@ohsu.edu
lab head
Phillip Wilmarth
contact affiliationOHSU
contact emailwilmarth@ohsu.edu
dataset submitter
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Dataset FTP location
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PRIDE project URI
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