{"doi":"10.14814/phy2.70519","title":"Convergent skeletal muscle cytokine responses to <scp>TFEB</scp> overexpression and voluntary wheel running reflect sex‐based variability to exercise adaptations in mice","abstract":"Running promotes skeletal muscle remodeling through metabolic and inflammatory signaling pathways, though the extent to which these responses are sex-dependent remains unclear. We profiled cytokine responses in quadriceps lysates from sedentary, voluntary wheel-running (VWR), and muscle-specific TFEB-overexpressing (cTFEB;HSACre) male and female mice. Cytokine analysis revealed 40 differentially expressed factors associated with exercise and/or TFEB overexpression, many exhibiting sex-dimorphic patterns. In males, VWR increased interleukins (IL-1α, IL-1β, IL-2, IL-5, and IL-17) and chemokines (e.g., MCP-1, CCL5, and CXCL9), including components of TNF signaling (e.g., TNFα, sTNFR1/2, and Fas ligand). These elevations were partially recapitulated by TFEB overexpression in sedentary males. In contrast, female VWR muscle showed limited changes, with significant differences restricted to IL-3, IL-3Rb, IL-13, and CXCL16. These findings demonstrate sex-specific cytokine responses to endurance-like stimuli and suggest a broader or more prolonged inflammatory remodeling profile in male skeletal muscle. Moreover, muscle-specific TFEB overexpression reproduced similar endurance-induced cytokine changes, particularly in males, highlighting TFEB as a partial molecular mimic of exercise-associated inflammatory signaling in skeletal muscle. Together, our data underscore the importance of sex as a biological variable in exercise-induced cytokine remodeling and support the utility of TFEB overexpression as a platform for prioritizing exercise-associated phenotypes.","journal":"Physiological Reports","year":2025,"id":526588,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":569974,"name":"Allison Birnbaum","orcid":"0000-0002-8904-3917","position":1,"is_corresponding":false},{"id":764067,"name":"Ian Matthews","orcid":null,"position":2,"is_corresponding":false},{"id":780211,"name":"Constanza J. Cortés","orcid":"0000-0002-6033-7428","position":3,"is_corresponding":false},{"id":985553,"name":"Dalton C. Patterson","orcid":"0000-0002-0208-7301","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T02:50:30.402772Z","pmid":"40834288","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":[]}