{"database":"iProX","file_versions":[],"scores":null,"additional":{"omics_type":["Proteomics"],"submitter":["Huang Yan"],"species":["Mus Musculus"],"full_dataset_link":["http://www.iprox.org/page/project.html?id=IPX0008850000"],"submitter_email":["yanhuang1018@csu.edu.cn"],"submitter_affiliation":["Xiangya Hospital of Central South University"],"sample_protocol":[""],"repository":["iProX"],"data_protocol":[""],"pubmed_abstract":["The benefits of exercise for metabolic health occur in a dose-dependent manner. However, the adverse effects of overtraining and their underlying mechanisms remain unclear. Here, we show that overtraining induces hepatic fibrosis. Mechanistically, we find that excessive lactate accumulation in skeletal muscle leads to the lactylation of SH3 domain-containing 3 (SORBS3), triggering its liquid-liquid phase separation (LLPS). LLPS of SORBS3 enhances its interaction with flotillin 1 and selectively facilitates the sorting of F-box protein 2 (FBXO2) into small extracellular vesicles, referred to as \"lactate bodies.\" Lactate bodies induce hepatocyte apoptosis followed by hepatic stellate cell activation via myeloid cell leukemia sequence 1 (MCL1)-BAX/BAK signaling. Inhibition of SORBS3 lactylation or FBXO2 disrupts lactate bodies formation and alleviates overtraining-triggered liver fibrosis. Likewise, reduction of muscle lactate bodies formation by salidroside attenuates overtraining-induced liver fibrosis. Collectively, we identify a process by which overtraining induces hepatic fibrosis, highlighting a potential therapeutic target for liver health."],"pubmed_title":["Muscle-derived small extracellular vesicles induce liver fibrosis during overtraining."],"pubmed_authors":["Liu Ya Y, Zhou Rui R, Guo Yifan Y, Hu Biao B, Xie Lingqi L, An Yuze Y, Wen Jie J, Liu Zheyu Z, Zhou Min M, Kuang Weihong W, Xiao Yao Y, Wang Min M, Xie Genqing G, Zhou Haiyan H, Lu Renbin R, Peng Hui H, Huang Yan Y"],"additional_accession":[]},"is_claimable":false,"name":"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.","dates":{"publication":"Tue May 21 00:00:00 GMT+01:00 2024"},"accession":"PXD052424","cross_references":{"TAXONOMY":["10090"],"pubmed":["39879982"]}}