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This Review synthesizes proteomic evidence on sepsis-associated alterations in proteins involved in metabolic pathways across circulating biofluids, immune cells, and organs. Across plasma and urine, proteomic studies identify disturbances in lipoprotein-associated pathways, redox homeostasis, mitochondrial function, and substrate metabolism, indicating that protein signatures of metabolic dysregulation are systemic and detectable across biofluids. In immune cells, monocytes and neutrophils, proteomic analyses reveal a shift toward glycolysis with concurrent impairment of mitochondrial pathways alongside phenotype-dependent differences in lipid and redox-related programs. Organ-level studies further show that metabolic responses are heterogeneous, with distinct trajectories in the kidney, heart, liver, lung, skeletal muscle, and brain. These observations support the concept that sepsis involves compartment-specific remodeling of metabolism-associated protein networks rather than a single convergent metabolic state. Proteomics also highlights potential translational opportunities by identifying metabolism-associated proteins linked to disease severity, clinical phenotypes, and biologically distinct patient subgroups, although the current evidence remains largely exploratory and context-dependent. Overall, proteomics provides a complementary framework for understanding the molecular regulation of sepsis-associated metabolic dysfunction and may refine biological stratification and therapeutic targeting, particularly when integrated with longitudinal sampling and multiomic data.<\/jats:p>","DOI":"10.1021\/acs.jproteome.6c00386","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T14:36:53Z","timestamp":1785854213000},"page":"4380-4392","source":"Crossref","is-referenced-by-count":0,"title":["Proteins as\nRegulators of Metabolic Changes in Sepsis:\nAlterations in Body Fluids, Immune Cells, and Organs through the Eyes\nof Proteomics"],"prefix":"10.1021","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1848-4480","authenticated-orcid":true,"given":"Giuseppe G. F.","family":"Leite","sequence":"first","affiliation":[{"name":"Universidade Federal de Sao Paulo , , ,","place":["Sa\u0303o Paulo, Brazil, 04039-032"]},{"name":"National Science and Technology Institute for Precision Critical Care Medicine\u2500INCT PCCM , ,","place":["Criciu\u0301ma, Brazil, 88806-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Dal-Pizzol","sequence":"additional","affiliation":[{"name":"National Science and Technology Institute for Precision Critical Care Medicine\u2500INCT PCCM , ,","place":["Criciu\u0301ma, Brazil, 88806-000"]},{"name":"University of Southern Santa Catarina (UNESC) , , , ,","place":["Criciu\u0301ma, Santa Catarina, Brazil, 88806-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"van der Poll","sequence":"additional","affiliation":[{"name":"National Science and Technology Institute for Precision Critical Care Medicine\u2500INCT PCCM , ,","place":["Criciu\u0301ma, Brazil, 88806-000"]},{"name":"University of Amsterdam , , ,","place":["Amsterdam, The Netherlands, 1105 AZ"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinaldo","family":"Saloma\u0303o","sequence":"additional","affiliation":[{"name":"Universidade Federal de Sao Paulo , , ,","place":["Sa\u0303o Paulo, Brazil, 04039-032"]},{"name":"National Science and Technology Institute for Precision Critical Care Medicine\u2500INCT PCCM , ,","place":["Criciu\u0301ma, Brazil, 88806-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"issue":"12","key":"2026090409123227500_cit1","doi-asserted-by":"publisher","first-page":"e2013","DOI":"10.1016\/S2214-109X(25)00356-0","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132021:\na systematic analysis","volume":"13","author":"Gray","year":"2025","journal-title":"Lancet Global Health"},{"issue":"7","key":"2026090409123227500_cit2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofae331","article-title":"Long-term mortality\nand hospital readmissions among survivors of sepsis in Sweden: a population-based\ncohort study","volume":"11","author":"Inghammar","year":"2024","journal-title":"Open Forum Infect. 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