Skeletal muscle secretes many signalisation proteins named myokines. These myokines act as hormones and induce metabolic changes throughout the whole body to facilitate adaptation to physical exercise. Interleukin-15 (IL-15) is highly expressed in skeletal muscle and appears to influence many metabolic parameters that are defective in metabolic pathologies such as insulin resistance. For instance, IL-15 increases glucose uptake in muscle and whole-body fatty acid oxidation and its overexpression in skeletal muscle in mice generates a very lean and active phenotype. However, there are discordant reports throughout scientific literature. The aim of the current study was to 1) characterize the metabolic effects of IL-15 in L6 myotubes to determine whether L6 is a good model to study IL-15 and 2) to determine whether IL-15 activates the AMPK signaling. L6 myotubes were exposed to different concentrations of IL-15 and different metabolic parameters were assayed namely; oxygen consumption, glucose uptake, fatty acid oxidation, Glucose transporter 4 (GLUT4) translocation, oxidative phosphorylation (OXPHOS) complexes protein expression, troponin T expression and Akt, AMPK and Acetyl-CoA Carboxylase (ACC) phosphorylation state. Acute IL-15 treatment increased glucose uptake without activating insulin signaling pathway or GLUT4 translocation. Furthermore, acute IL-15 treatment increased resting oxygen consumption rate (OCR) while chronic IL-15 treatment also increased mitochondrial spare capacity, suggesting an increased mitochondrial biogenesis. IL-15 induced ACC phosphorylation in a dose-dependent manner and tended to increase AMPK phosphorylation but it did not reach statistical significance. Lastly, IL-15 did not influence troponin T state. Altogether, the present study demonstrates that L6 myotubes do not express all the pro-oxidative qualities of IL-15 reported by scientific literature. Nonetheless, IL-15 induces certain pro-oxidative metabolic effect that could help people living with obesity and diabetes.

Background: Exercise in pregnancy is associated with optimized fetal growth; however, the implicated mechanisms remain unknown. We hypothesize that exercise-induced myokines may be acting on the placenta to optimize fetal growth across gestation. Methodology: 1) Circulating profiles of 11 myokines were analyzed in 2nd trimester plasma of women characterized as active (N=14) or non-active (N=16) during pregnancy. 2) First trimester human placental explants (N=5) were treated with SPARC in a dose-dependent manner (0-150ng/ml). Metrics of placental health/function, including GLUT-4 expression/regulation, were assessed. Results: 1) Active women demonstrated an elevation in circulating SPARC compared to non-active women (86±19pg/ml vs. 52±18pg/ml, p=0.0001). 2) Explants treated with SPARC at 100ng/ml demonstrated improved invasion, with improved maximum outgrowth distance (N=3; p=0.0219). Conclusion: SPARC is a myokine that is elevated in the circulation of active pregnant women and is associated with improved placental invasion, suggesting a possible role of SPARC in placentation.

Background: It is well established throughout the literature that regularly engaging in physical activity throughout pregnancy is associated with optimized health outcomes for both the mother and the fetus. The mediators and mechanistic pathways through which these observed exercise-induced outcomes are achieved are largely unknown. This thesis attempts to address this gap in knowledge. Methods: The objective of the first study was to develop an exercise protocol based on the recommendations from the ‘2019 Canadian guideline for physical activity throughout pregnancy’ and to subsequently evaluate the myokine response post-exercise. Pregnant (n=13) and non-pregnant (n=17) women performed a moderate-intensity bout of treadmill walking following which pre- and post-exercise serum for a panel of ten well-characterized myokines was analyzed. The objective of the second study was to evaluate whether acute and/or chronic exercise elicited changes in metrics of placental growth and development – thereby proposing possible mechanisms through which physical activity may be conferring health benefits to the fetus. Serum (pre- and post-exercise) collected from the first study was used to treat placental cell lines to assess the effect of acute exercise on cellular proliferation as well as nutrient transporter (GLUT1, SNAT1, FATP4) expression and localization. Term placental tissue collected from active (n=10) and non-active (n=10) participants in the PLACENTA study were used to evaluate the role of chronic exercise on changes in nutrient transporter (GLUT1, SNAT1, FATP4) expression and localization. Results: Pregnant women from the first study exhibited higher levels of four myokines post- versus pre-exercise: FGF21, EPO, BDNF and IL-15. As for the second study, BeWo cell lines treated with serum collected from pregnant women yielded higher GLUT1 expression compared to non-pregnant serum, independently of exercise. Lastly, FATP4 expression was found to be higher in term placentas of active compared to non-active pregnant women. Conclusion: This thesis identified four myokines that are elevated in the serum of pregnant women following a bout of acute exercise. The role of these myokines in pregnancy remains to be elucidated. Further, chronic and acute exercise are shown to alter expression of key placental macronutrient transporters.

BACKGROUND: Colorectal cancer incidence and mortality rates are rising and are still one of the most common cancers worldwide. Its risks are associated with the Western Lifestyle, important facets of this being increase physical inactivity and excess body weight. In sync with colorectal cancer’s increasing rates are obesity rates that are rising in both developed and developing countries. Obesity has been linked to several causes of death that includes cardiovascular disease and certain cancers. Studies have shown the benefits of exercise overtly in alleviating cardiovascular diseases but now have increasing evidence of its benefits in helping with cancer. Some studies have examined the effects of physical activity in colon cancer and have found a link between increase minutes of exercise weekly can slow cancer cell proliferation in colon crypts cells. Myokines are a newly discovered class of proteins that are produced by muscles and have multiple functions. One of those function is its anti-neoplastic activity against certain cancer cell types. Certain myokines evoke an anti-neoplastic effect on cancer, but there has not been an overwhelming agreement within the scientific community. OBJECTIVE: To investigate the anti-proliferative effects of exercise myokines produced by C2C12 cells in colorectal cancer cell lines: HCT116 and HT29, by looking at changes in protein expression through western blot analysis and protein arrays. METHODS: C2C12 cells were grown in cell culture plates and differentiated into myotubules. Myotubules were subjected to Electronic Pulse Stimulation using an apparatus called C-Pace by Ion Optix to generate myokines. Treat HCT116 and HT29 cell lines with exercise myokines and a control treatment and ultimately harvest their protein lysate for western blot analysis and protein array analysis. RESULTS: HCT116 treated with exercise myokines with different dilutions (1:25, 1:50, 1:100) a demonstrated significantly decreased proliferation (p<0.0001). HT29 treated with exercise myokines (1:25 dilution) also demonstrated a significant decrease in proliferation (p<0.0001). Western blot analysis of HCT116 treated with exercise myokines showed significantly lower expression in pRb (p<0.05), PCNA (p<0.05), and cyclin D1 (p<0.05). Western blot analysis of HT29 treated with exercise myokines revealed significant expression downregulation in exercise myokine treatment in PCNA (p<0.05), p42/p44 (p<0.05), pRb (p<0.0001) and Cyclin D1 (p<0.05). Human Phospho-Kinase Array demonstrated downregulation of the following proteins in HT29 cells treated with exercise myokines: GSK-3α/β, STAT3, EGFR, p53, PDGF Rβ, Src, PRAS40, WNK1, and JNK 1/2/3. Lastly, HT29 treated with exercise myokines showed downregulation of the p-EGFR and pHGFR as a result of the Human Phospho-RKT Array. CONCLUSION: Our data demonstrate that exercise myokines produced by Electric Pulse Stimulation of C2C12 cells have an anti-proliferative effect on colorectal cancer cell lines HCT116 and HT29. Further studies should be pursued to identifying and linking anti-proliferative properties to a specific myokine protein and confirming a pathway that this specific myokine exerts its effects.

Breast cancer the second most common cancers in women. A weight gain, higher amount of adipose tissue and lower physical activity are risk factors for breast cancer in terms of nutritional status. Recent studies document a negative effect of adipokines, adipose tissue hormones on the development and prognosis of cancer. Likewise, the positive effect of myokines, hormones of muscle tissue, has been increasingly discussed in recent years. Influencing the amount of adipose and muscle tissue in the body is possible through nutritional and physical intervention. A cooperation with a dietitian was offered to 81 patients in the Masaryk Memorial Cancer Institute. The offer of nutritional and physical intervention was accepted by 25 patients and 19 patients completed 3 months of therapy. The aim of the study was to analyze the development of weight in patients before and after the diagnosis of breast cancer, and futher to perform a nutritional intervention in the form of a 3 - month program using personal visits and online monitoring of diet and physical activity and to characterize the diet in patients with breast cancer after the intervention. From the obtained data it was not possible to perform an analysis of weight development in patients. The performed evaluation of eating habits based on a comparison...

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High intensity exercise is believed to yield greater results on health and human performance than moderate intensity exercise. Extensive research indicates that not only do high-intensity interval training (HIT) and sprint interval training (SIT) produce significant improvements in cardiovascular fitness and disease, they may be more effective at improving long-term metabolic function, including insulin sensitivity (Si), by producing more mitochondria. Moreover, compliance rates for HIT and SIT participation are reported to be the same or better than traditional moderate intensity exercise. Because lack of time is often cited as major hindrance to exercise participation, SIT is also seen as a time efficient option to improve health and performance. It does appear, however, that repeated sessions of SIT are needed before overall improvements can be measured. SIT protocols employing maximal 30 sec sprints with ~5 min rest [a 1:9 work-to-rest ratio (W:R)], have garnered much of the research focus, while those using minimal rest periods, like Tabata which uses 20 sec sprints and 10 sec rest (2:1 W:R), have been ignored. This may omit a possible SIT option that could influence acute and chronic adaptations. The role of inflammatory cytokines on Si remains an area of continued research. While endurance exercise is thought to create an overall anti-inflammatory environment that stimulates improvement in Si, SIT is often viewed as pro-inflammatory. However, few studies have provided significant insight into cytokine release following SIT, and none haveexplored its impact on Si. In addition, the impact of W:R on cytokine remains speculative at best. Therefore, the examination of the effect of different sprint protocols of similar total work (kJ) on performance, metabolic function, and inflammatory response may provide valuable insight into these adaptive processes.