EXERCISE-INDUCED MYOKINES RELEASE: IMPACT ON PERFORMANCE AND MENTAL HEALTH IN HEALTH AND DISEASE

Physical exercise exerts profound systemic effects on human physiology, mediated by the secretion of signalling molecules such as myokines, adipokines, and neuropeptides. These factors regulate energy metabolism, tissue repair, neuroendocrine function, and overall homeostasis, thereby contributing to the well-documented benefits of regular training on health and performance. However, the acute responses of these molecules remain incompletely understood, particularly in resistance-trained individuals and in relation to exercise modality, intensity, and individual characteristics such as age and physical fitness. This doctoral thesis aimed to address this gap by examining the acute biochemical and perceptual responses to resistance and aerobic exercise under different conditions, focusing on irisin, adiponectin, and β-endorphins, alongside traditional markers of muscle damage and perceived soreness. The thesis comprises five studies, including four experimental investigations in trained men and one exploratory pilot study in breast cancer survivors, providing novel insights into the regulation of these molecules and their relevance to training prescription and health. The first study investigated the acute response of irisin to an exhaustive resistance training protocol in young, resistance-trained men. Participants completed a whole-body routine performed to volitional failure, with blood samples collected at baseline, 15 min, 24 h, and 48 h post-exercise. The findings showed a transient increase in irisin alongside a substantial elevation in creatine kinase (CK), confirming muscle damage. Although irisin responses were heterogeneous and not temporally associated with CK dynamics, the data suggest that irisin release is not simply a by-product of muscle disruption but may instead reflect broader systemic or metabolic regulation. The second study replicated the analysis under a buffered resistance training condition, in which sets were terminated with two repetitions in reserve. This protocol elicited lower CK elevations and reduced muscle soreness compared with exhaustive training. Irisin again demonstrated a modest but consistent increase, confirming its lack of association with muscle damage. Together, these first two studies, aligned with previously published evidence, indicate that irisin responses to resistance training in trained individuals are modest compared with those elicited by aerobic exercise. The third study shifted focus to adiponectin, a key adipokine linked to insulin sensitivity and metabolic health. Participants performed two resistance training protocols (exhaustive and buffered). Contrary to evidence from obese or metabolically compromised populations, both conditions induced significant and sustained decreases in circulating adiponectin concentrations, persisting up to 48 h post-exercise. This suppression occurred irrespective of training to failure or to reserve. These findings support the hypothesis that in healthy, resistance-trained individuals with presumably optimal baseline levels, exercise induces receptor-level or tissue-specific adaptations rather than elevations in systemic adiponectin. The results highlight the population and context-specific nature of adiponectin regulation and caution against generalising findings from clinical cohorts to trained athletic populations. The fourth study broadened the scope by examining the neuroendocrine response of β-endorphin (β-EDP) to a maximal incremental cycling test in a heterogeneous cohort of men aged 20–65 years. Blood samples collected at baseline, 15 min, and 24 h post-exercise revealed a robust but transient β-EDP increase, followed by a return toward baseline within 24 h. Younger adults exhibited higher baseline and post-exercise concentrations than middle-aged men, although high physical fitness attenuated this age-related decline. Middle-aged individuals with excellent fitness displayed β-EDP levels comparable to those of younger adults with good fitness, underscoring the protective role of fitness in preserving neuroendocrine responsiveness across the lifespan. This study provides novel evidence that age exerts a stronger influence than fitness on baseline β-EDP concentrations, while fitness can partially offset age-related reductions. The fifth and final pilot study extended the investigation to a clinical context, exploring salivary irisin responses to aerobic exercise in breast cancer survivors. Participants completed both an acute moderate-intensity exercise session and an eight-week supervised training programme. Despite the small sample size, salivary irisin concentrations consistently increased 24 hours post-exercise, particularly after the training period, alongside improvements in aerobic capacity, flexibility, and body composition. These preliminary findings demonstrate the feasibility of non-invasive biomarker monitoring in oncological populations and suggest that moderate aerobic exercise may exert favourable molecular and functional effects deserving confirmation in larger cohorts. Taken together, the five studies contribute new evidence on the acute regulation of myokines, adipokines, and neuropeptides in response to exercise. The data demonstrate that: (I) irisin responses to resistance training are moderate, heterogeneous, and independent of muscle damage; (II) adiponectin decreases following resistance training in trained men, contrary to findings in clinical cohorts; (III) training to failure induces greater muscle damage and soreness but does not confer superior endocrine benefits over buffered training; (IV) β-endorphin responses to aerobic exercise are strongly shaped by age, with fitness acting as a mitigating factor; and (V) moderate-intensity aerobic exercise in breast cancer survivors may promote favourable modulation of salivary irisin, supporting the feasibility of saliva-based biomarker monitoring in clinical research. Theoretically, these findings challenge simplified models of exercise-induced cytokine regulation and emphasise the need to consider population characteristics, training status, and exercise modality when interpreting biomarker dynamics. Practically, the work suggests that submaximal resistance training may represent a more sustainable strategy than training to failure, balancing adaptation with recovery, while aerobic exercise confirms its importance for preserving neuroendocrine function during ageing and supporting functional recovery in clinical populations. In summary, this doctoral thesis demonstrates that acute exercise exerts multifaceted effects on circulating signalling molecules, muscle damage, and subjective perception, shaped by both external factors (modality, intensity) and internal characteristics (age, fitness). By integrating biochemical, physiological, and perceptual perspectives, the work advances a more nuanced understanding of how acute exercise challenges human physiology. It highlights the limitations of relying on single biomarkers as proxies for adaptation and underscores the need for integrative approaches in both research and practice. Ultimately, these findings provide a conceptual framework for optimising training strategies in health, performance, and ageing.