Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C072

Oral Communications

The impact of acute exercise upon myokine secretion in rat models outbred for either low or high aerobic capacity in response to treadmill run training

W. F. Farrash1,3, B. E. Phillips4,2, S. L. Britton4, L. G. Koch5, D. Wilkinson1,2, K. Smith1,2, P. J. Atherton1,2

1. MRC-ARUK Centre for Musculoskeletal Ageing Research, Clinical, Metabolic and Molecular Physiology, University of Nottingham, Derby, United Kingdom. 2. Nottingham NIHR BRC, Derby, United Kingdom. 3. Applied medical sciences, Umm Al-Qura University, Makkah, Saudi Arabia. 4. Department of Anesthesiology, University of Michigan, Michigan, Michigan, United States. 5. Department of Physiology and Pharmacology, University of Toledo, Toledo, Ohio, United States.

Introduction: Exercise causes skeletal muscles to express and secrete myokines, that in turn stimulate autocrine/paracrine, and endocrine activities. Myokines secreted from muscle are purported to promote adaptations (e.g. mitochondrial biogenesis ((1) and trans-organ cross-talk to exert numerous beneficial effects of exercise upon health (2). Nonetheless, the functional role of myokines in governing exercise adaptation is ill defined. To address this, we adopted ‘low responder trainer' (LRT) and ‘high responder trainer' (HRT) rat models to compare myokine responses to acute exercise. We hypothesised that HRT animals would display greater myokine secretion than LRT reflecting differences in adaptive potential. Methods: LRT and HRT (N=8) rats were selectively bread for low/high adaptive capacity to running training (3). Blood was collected at baseline and then immediately, 1h, and 3h after a bout of running exercise. Plasma was analysed using targeted proteomics by multiplex ELISA to concurrently quantify 12 myokines: BDNF, FGF21, Fractalkine, IL-6, IL-15, Irisin, Erythropoietin, FSTL-1, Myostatin, LIF, SPARC, and Osteocrin. Data were analysed by ANOVA and Bonferroni tests; P<0.05 being significant. Results: BDNF and FSTL-1 exhibited no changes in concentration after exercise. However, Myostatin, IL-15, and Fractalkine concentrations declined 3h post-exercise in both LRT (P=0.039 (30%), P=0.004 (12%), P=0.012 (40%) respectively)) and HRT (P=0.025 (20%), P=0.008 (10%), P=0.004 (40%) respectively) animals. Similarly, plasma Irisin paradoxically declined by ~20% at 1h post-exercise, only in LRT animals (P=0.032). In contrast, IL-6 and LIF increased at 3h post-exercise in both LRT (P=0.02 (130%), P= 0.027 (20%) respectively)) and HRT (P=0.0004 (310%), P=0.016 (20%) respectively)). In addition in the HRT group only, FGF21 was approximately doubled post exercise (at 0 and 3h, P<0.05), Erythropoietin levels also increased by ~20% at 3h (P=0.023), whereas SPARC was elevated by ~50% immediately after exercise (P=0.016). No myokines demonstrated a significant interaction in the two-way ANOVA, except Osteocrin (P= 0.004), where LRT animals exhibited a greater increase than HRT. Conclusion: Our results revealed some anticipated "exercise responses" for established myokines e.g. IL-6/LIF increasing and Myostatin decreasing, while IL-15/Irisin paradoxically dropped. Across models, there were only subtle differences including moderate temporal increases in FGF21, Erythropoietin and SPARC specific to HRT animals. Osteocrin was higher at baseline, increased significantly immediately post exercise and remained higher throughout in the LRT. We conclude that while differences exist in myokine secretion, in LRT vs. HRT, these differences are subtle and seem unlikely to drive the extreme phenotypic metabolic adaptations to exercise in LRT vs. HRT animals.

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