{"doi":"10.1016/j.clnesp.2024.02.024","title":"Changes in proteomic cargo of circulating extracellular vesicles in response to lifestyle intervention in adolescents with hepatic steatosis","abstract":"BACKGROUND: Recent studies suggest that proteomic cargo of extracellular vesicles (EVs) may play a role in metabolic improvements following lifestyle interventions. However, the relationship between changes in liver fat and circulating EV-derived protein cargo following intervention remains unexplored. METHODS: The study cohort comprised 18 Latino adolescents with obesity and hepatic steatosis (12 males/6 females; average age 13.3 ± 1.2 y) who underwent a six-month lifestyle intervention. EV size distribution and concentration were determined by light scattering intensity; EV protein composition was characterized by liquid chromatography tandem-mass spectrometry. RESULTS: Average hepatic fat fraction (HFF) decreased 23% by the end of the intervention (12.5% [5.5] to 9.6% [4.9]; P = 0.0077). Mean EV size was smaller post-intervention compared to baseline (120.2 ± 16.4 nm to 128.4 ± 16.5 nm; P = 0.031), although the difference in mean EV concentration (1.1E+09 ± 4.1E+08 particles/mL to 1.1E+09 ± 1.8E+08 particles/mL; P = 0.656)) remained unchanged. A total of 462 proteins were identified by proteomic analysis of plasma-derived EVs from participants pre- and post-intervention, with 113 proteins showing differential abundance (56 higher and 57 lower) between the two timepoints (adj-p <0.05). Pathway analysis revealed enrichment in complement cascade, initial triggering of complement, creation of C4 and C2 activators, and regulation of complement cascade. Hepatocyte-specific EV affinity purification identified 40 proteins with suggestive (p < 0.05) differential abundance between pre- and post-intervention samples. CONCLUSIONS: Circulating EV-derived proteins, particularly those associated with the complement cascade, may contribute to improvements in liver fat in response to lifestyle intervention.","journal":"Clinical Nutrition ESPEN","year":2024,"id":434864,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.805,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":338824,"name":"Ignazio S. Piras","orcid":"0000-0003-4024-3368","position":1,"is_corresponding":false},{"id":442155,"name":"Xiumei Wu","orcid":"0000-0002-9469-5450","position":2,"is_corresponding":false},{"id":341886,"name":"Ritin Sharma","orcid":"0000-0001-8365-9916","position":3,"is_corresponding":false},{"id":340880,"name":"Krystine Garcia‐Mansfield","orcid":null,"position":4,"is_corresponding":false},{"id":1241622,"name":"Maya Willey","orcid":"0009-0003-8282-4643","position":5,"is_corresponding":false},{"id":1242067,"name":"Brooke Lovell","orcid":null,"position":6,"is_corresponding":false},{"id":339633,"name":"Patrick Pirrotte","orcid":"0000-0003-1360-6039","position":7,"is_corresponding":false},{"id":516468,"name":"Micah L. Olson","orcid":"0000-0002-9182-961X","position":8,"is_corresponding":false},{"id":334002,"name":"Gabriel Q. Shaibi","orcid":"0000-0002-6890-2903","position":9,"is_corresponding":false},{"id":242511,"name":"Johanna K. DiStefano","orcid":"0000-0002-3286-0270","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T01:59:58.582186Z","pmid":"38479932","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}