PXD052424-1

PXD052424 is an original dataset announced via ProteomeXchange.

Title	Muscular lactate modulates phase transition-driven lactate body secretion to induce liver fibrosis during long-term overtraining
Description	Exercise, as the fundamental therapy for metabolic diseases, often exhibits a dose-dependent fashion. However, the adverse effects of overtraining and underlying mechanisms remain unclear. Here, we show that long-term overtraining induces hepatic fibrosis in humans and mice. Mechanistically, excessive lactate accumulation in skeletal muscle renders SH3 domain containing 3 (SORBS3) lactylation, triggering the liquid-liquid phase separation (LLPS) of SORBS3. LLPS of SORBS3 enhances the interaction with flotillin 1 (FLOT1) and selectively facilitates the sorting of F-Box Protein 2 (FBXO2) into specific exosome, named as ‘lactate body’, which induces hepatocyte apoptosis and hepatic satellite cell activation. Inhibition of the SORBS3 lactylation disrupts lactate body formation and alleviates the overtraining-triggered liver fibrosis. Of importance, serum lactate levels are positive-associated with exercise intensity and lactate body levels in mice and humans. Collectively, we identify a novel mechanism of selective loading of exosome cargos, and the inter-tissue communication between muscle and liver during overtraining.
HostingRepository	iProX
AnnounceDate	2024-05-21
AnnouncementXML	Submission_2026-08-19_22:54:07.273.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhou Rui
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-20 20:01:44	ID requested
⏵ 1	2026-08-19 22:54:08	announced

Liu Y, Zhou R, Guo Y, Hu B, Xie L, An Y, Wen J, Liu Z, Zhou M, Kuang W, Xiao Y, Wang M, Xie G, Zhou H, Lu R, Peng H, Huang Y, Muscle-derived small extracellular vesicles induce liver fibrosis during overtraining. Cell Metab, 37(4):824-841.e8(2025) [pubmed]

submitter keyword: lactate, liver fibrosis, overtraining, exosome

Huang Yan
contact affiliation	Xiangya Hospital of Central South University
contact email	yanhuang1018@csu.edu.cn
lab head
Zhou Rui
contact affiliation	Xiangya Hospital of Central South University
contact email	218111003@csu.edu.cn
dataset submitter

iProX dataset URI