{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T07:44:33Z","timestamp":1775979873983,"version":"3.50.1"},"posted":{"date-parts":[[2025,5,28]]},"group-title":"Physiology","reference-count":42,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T00:00:00Z","timestamp":1748390400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["RF1 AG057264 - 03W1"],"award-info":[{"award-number":["RF1 AG057264 - 03W1"]}]},{"name":"National Institute of Health","award":["T32 AG052374"],"award-info":[{"award-number":["T32 AG052374"]}]},{"name":"National Institute of Health","award":["R01 AG077536"],"award-info":[{"award-number":["R01 AG077536"]}]},{"DOI":"10.13039\/100000957","name":"Alzheimer\u2019s Association","doi-asserted-by":"crossref","award":["AARF-21-851362"],"award-info":[{"award-number":["AARF-21-851362"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Endurance exercise (running) promotes skeletal muscle remodeling through metabolic and inflammatory signaling cascades. However, the extent to which these responses are sex-dependent remains unclear. Here, we profiled cytokine responses in quadriceps muscle lysates from sedentary, voluntary wheel-running (VWR; 5 weeks), 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 displaying sex-dimorphic expression patterns. In males, VWR induced significant increases in interleukins (e.g., IL-1\u03b1, IL-1\u03b2, IL-2, IL-5, IL-17) and chemokines (e.g., MCP-1, CCL5, CXCL9), as well as cytokines involved in TNF signaling (e.g., TNF\u03b1, sTNFR1\/2, Fas ligand). TFEB overexpression in sedentary males recapitulated many of these cytokine elevations. In contrast, female runner muscle showed limited cytokine activation, with significant changes restricted to IL-3, IL-3Rb, IL-13, and CXCL16. Both sexes exhibited a reduction in IL-4 and an increase in IGFBP-5 with running. Several additional male-specific cytokine profiling responses, including increases in IFN\u03b3, SCF, TPO, VCAM1A, and leptin, further underscored the sex-specificity of exercise-related inflammatory adaptations. These findings demonstrate that skeletal muscle cytokine responses to endurance-like stimuli are profoundly influenced by sex and suggest that male muscle exhibits a broader and\/or later remodeling profile than female muscle. Our data also implicate skeletal muscle TFEB-overexpression as a partial molecular mediator of the cytokine shifts observed with exercise, particularly in males, and highlights their potential use as a new prioritization platform for exercise-associated phenotypes.<\/jats:p>","DOI":"10.1101\/2025.05.28.655862","type":"posted-content","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T05:20:23Z","timestamp":1748496023000},"source":"Crossref","is-referenced-by-count":0,"title":["Convergent Skeletal Muscle Cytokine Responses to TFEB Overexpression and Voluntary Wheel Running Reflect Sex-Based Variability in Exercise Adaptations"],"prefix":"10.64898","author":[{"given":"Dalton C.","family":"Patterson","sequence":"first","affiliation":[{"name":"Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294, 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