PXD063124

PXD063124 is an original dataset announced via ProteomeXchange.

Title	Intermittent Fasting Drives Metabolic Reprogramming Through Tissue-Specific and Shared Molecular Adaptations
Description	Intermittent fasting (IF) has emerged as a powerful dietary intervention with significant metabolic benefits, yet the tissue-specific molecular mechanisms underlying these effects remain poorly understood. In this study, we employed a multi-omics approach, integrating proteomics and transcriptomics, to investigate the systemic and organ-specific adaptations to IF in male C57BL/6 mice. Following a 16-hour daily fasting regimen (IF16) over four months, IF significantly reduced blood glucose, HbA1c, and cholesterol levels while increasing ketone bodies, indicative of enhanced metabolic flexibility. Proteomic profiling of the liver, muscle, and cortex revealed tissue-specific responses, with the liver exhibiting the most pronounced changes, including upregulation of pathways involved in fatty acid oxidation, ketogenesis, and glycan degradation, alongside downregulation of steroid hormone biosynthesis and cholesterol metabolism. In muscle, IF’s proteomic profile indicates enhanced pyruvate metabolism, fatty acid biosynthesis, and AMPK signaling, while suppressing oxidative phosphorylation and thermogenesis. The cortex displayed unique adaptations, with upregulation of autophagy, PPAR signaling, and metabolic pathways, coupled with downregulation of TGF-beta and p53 signaling, suggesting a shift toward energy conservation and stress resilience. Notably, Serpina1C emerged as the only protein commonly upregulated across all three tissues, highlighting its potential role in systemic adaptation to IF. Integrative transcriptomic and proteomic analyses revealed partial concordance between mRNA and protein expression, underscoring the complexity of post-transcriptional regulation. Shared biological processes, such as synaptic vesicle localization, were identified across tissues, suggesting a unifying mechanism linking metabolic changes to cellular communication. These findings provide a comprehensive map of the molecular adaptations to IF, revealing both conserved and tissue-specific responses that optimize energy utilization, enhance metabolic flexibility, and promote cellular resilience. This study advances our understanding of the physiological benefits of IF and highlights potential therapeutic targets for metabolic and neurodegenerative disorders.
HostingRepository	PRIDE
AnnounceDate	2026-03-18
AnnouncementXML	Submission_2026-03-18_04:49:38.233.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Rohan Lowe
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-19 06:08:55	ID requested
⏵ 1	2026-03-18 04:49:38	announced

10.7554/ELIFE.107332.1;

submitter keyword: Intermittent Fasting, Bioinformatics, Metabolic reprogramming, Transcriptomics, Serpina1c, Proteomics

Thiruma V. Arumugam
contact affiliation	Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science and Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, VIC, Australia
contact email	g.arumugam@latrobe.edu.au
lab head
Rohan Lowe
contact affiliation	La Trobe University
contact email	r.lowe@latrobe.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/2026/03/PXD063124

PRIDE project URI

• PRIDE
  1. PXD063124
     1. Label: PRIDE project
     2. Name: Intermittent Fasting Drives Metabolic Reprogramming Through Tissue-Specific and Shared Molecular Adaptations