PXD067874-1

PXD067874 is an original dataset announced via ProteomeXchange.

Title	Understanding how reduced energy intake rapidly alleviates obesity associated insulin resistance
Description	Insulin resistance (IR) underpins the relationship between obesity and its associated metabolic disorders. Negative energy balance alleviates IR rapidly, though the mechanism remains unclear. Here, we show that in obese mice, IR can be reversed by calorie reduction (CR) within a day. In the liver, improved insulin sensitivity correlates with reduced tri-(TAG) and diacylglycerol (DAG) concentrations and decreased protein kinase C epsilon (PKCε) activation. In muscle, insulin-stimulated glucose disposal was also restored, whereas obesity-related changes in adipose tissue largely persisted following CR. Specifically, obesity is associated with reduced fasting lipolytic activity in adipose tissue, likely mediated in part by lower beta-adrenergic receptor 3 (ADRB3) expression. Acute CR did not reverse these adipose changes but further reduced plasma free fatty acid (FA) levels by dampening lipolytic activity and upregulating oxidative pathways in muscle and liver. This facilitates insulin-stimulated glucose disposal and restores insulin sensitivity.
HostingRepository	PRIDE
AnnounceDate	2026-06-08
AnnouncementXML	Submission_2026-06-07_17:45:59.387.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaowen Duan
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-29 05:04:01	ID requested
⏵ 1	2026-06-07 17:46:00	announced

10.1126/sciadv.aed0535;

Duan X, Davis LM, Patel S, Bidault G, Long L, Jenkins B, Yi Y, Pushpa P, Wesseling JR, Koulman A, Vidal-Puig A, Fazakerley DJ, Savage DB, Integrated analysis of insulin resistance reveals metabolic remodeling following diet switch-triggered calorie reduction. Sci Adv, 12(19):eaed0535(2026) [pubmed]

submitter keyword: insulin resistance, calorie restriction,obesity

David Savage
contact affiliation	Institute of Metabolic Science, University of Cambridge
contact email	dbs23@cam.ac.uk
lab head
Xiaowen Duan
contact affiliation	Institute of Metabolic Science
contact email	xd253@cam.ac.uk
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/2026/06/PXD067874

PRIDE project URI

• PRIDE
  1. PXD067874
     1. Label: PRIDE project
     2. Name: Understanding how reduced energy intake rapidly alleviates obesity associated insulin resistance