Circulating Extracellular Vesicle Characteristics Differ Between Men And Women Following 12-weeks Of Concurrent Exercise Training.

Concurrent resistance and endurance exercise training (CET) have numerous health benefits; however, hormonal and genetic differences exist that alter responses to CET between sexes. These include greater muscle mass, type II fiber area and higher release of IL-6 and testosterone following exercise in men. Extracellular vesicles (EVs) contribute to the adaptive signaling environment following exercise. Little is known of the EV response to concurrent exercise training in men and women. PURPOSE: To determine if EV characteristics differ between men and women following acute and chronic CET. METHODS: 18 participants (age: 27.3, Body fat: 27.8%, female n = 9) underwent 12-weeks of CET consisting of resistance followed by interval training. Prior to and following the CET, subjects performed an acute bout of heavy resistance exercise (AHRET). Blood was taken at rest and following AHRET. EVs were isolated from plasma via size-exclusion chromatography. EV concentration, size, surface markers, and miRNA contents were analyzed via nanosight tracking analysis, imaging flow cytometry, and small RNA sequencing respectively. Data were analyzed via three-way [Sex x AHRET x chronic training] repeated-measures analysis of variance (ANOVA), significance: p = 0.05. RESULTS: AHRET elevated circulating [EV] (+51%, p = 0.04) and EV protein content (+108%, p = 0.02) in trained men only. AHRET decreased muscle-derived (SGCA+) EVs (1.05% vs 0.52%, p = 0.02) and increased microvesicles (VAMP3+) EVs (2.5% vs 3.1% p = 0.02). There were considerable sex-specific effects of CET on EV miRNAs, highlighted by greater miRNA in women (2,852 pg/ml vs 1,208 pg/ml p = 0.01) and a larger variation in differentially expressed EV miRNAs at rest following CET in men (39 vs 12). This pattern was inverted following AHRET (7 vs 32). Pathway analysis predicted that AHRET and 12-weeks of CET in men positively regulates resistance training related pathways (including PI3K/Akt, mTOR, IGF-1 and IL-6 signaling pathways) more so than in women. CONCLUSIONS: AHRET increased EVs following 12 weeks of CET in men only. EV markers are sensitive to AHRET independent of sex and training. Lastly, EV miRNA contents differ greatly between men and women and exercise training causes miRNA contents to be more supportive of exercise related pathways in men compared to women. UKMOD, Award No. WGCC 5.5.6